bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study: Impact of a non‐weight loss intervention, focused on changing diet and physical activity (PA) behaviors, in midlife women at risk for metabolic syndrome (MetS)
Authors: Pilolla K D , Bryant T K , Manore M M , Donatelle R J , Jabson J M , Walker A J , Ourada V E
Published: June 2021

The purpose of this pilot study was to determine if a 12‐wk diet, exercise and lifestyle intervention, which was not focused on weight loss, could improve diet and PA, while reducing risk factors for MetS in high risk midlife women. This approach reduced the stress of weight loss, while focusing on healthy behaviors known to reduce MetS. 10 sedentary overweight midlife women (mean ± SD: age=47±3y; BMI=31.0±3.1kg/m2; waist circumference=41.1±3.5in) at risk for MetS were recruited. At pre and post‐intervention subjects completed diet history and PA questionnaires, 4‐d weighted food records/PA logs. The intervention was focused on increasing whole grains, fruits and vegetables (ser/d), reducing saturated fat (g/d) and increasing PA (min/d) to improve blood lipids (total cholesterol [Chol], High Density Lipoprotein‐Chol, Low Density Lipoprotein‐Chol, triglycerides), C‐reactive protein and blood pressure. Results showed an increase in whole grains (Δ=2.6 ser/d) and PA (Δ=39 min/d), and a decrease in saturated fat (Δ=7.5 g/d) (P<0.05). Fruit, vegetable and total fat intake did not change significantly and there were no significant improvements in MetS risk factors. Overall the program was successful in increasing PA, but dietary changes were less impressive. Weight loss may be necessary to see changes in the risk factors examined at 12‐wks, and/or the intervention needs to be longer. Funded by OSU‐HHS.
Acceptability by a low income audience of a low cost two week cycle menu that meets the food recommendations of the 2005 Dietary Guidelines for Americans
Authors: Mullenix Anna , Zanovec Michael , Stewart Laura J. , O'Neil Carol E.
Published: June 2021

The purpose of this study was to plan a low‐cost two week cycle menu with foods/recipes tailored to tastes of Southeast Louisiana that met the 2005 Dietary Guidelines (DGA) for a family of four (male, female, two children) and to test its acceptability by a regional low‐income audience. Menus, costing an average of $616/week (mean price from 29 regional grocery stores), met the energy and food recommendations of the DGA, but differed substantially from the usual intake of this population since they included more whole grains, beans, fruit, vegetables, and dairy than are commonly consumed by this population. To test acceptability, two groups of low‐income individuals were interviewed. Group 1 (n=8; 100% female; 63% black) and group 2 (n=12; 75% female; 100% black) were questioned about acceptability of and barriers to consuming these menus. Group 1 was older (38.6±7.4y [SD]) and had more children (4.25±2.4) than Group 2 (23.8±10.8, 0.25±0.62) (p<0.001 for both); unlike Group 2, Group 1 had nutrition education through EFNEP and a better understanding of nutrition. They stated that they liked fruit and vegetables more, and found the menus feasible and much more acceptable than Group 2. Group 2 wanted to substitute more nutrient dense foods into the menus. Both groups generally wanted larger portion sizes and fewer legumes. Taste and lactose intolerance were the principal barriers to acceptability. Support: ERS Small Grant.
Large Percentage of Young Black Adults Have Risk Factors for Coronary Heart Disease in South Florida
Authors: Davis Errol E , Huffman Fatma G
Published: June 2021

Objective: To investigate risk factors for CHD in young Black adults and, to determine and compare these risk factors in 91 Black males and 98 Black females ages 18–40 years in a cross‐sectional analysis. Socio‐demographic, dietary, physical activity, anthropometric, cigarette smoking and biochemical data were collected and analyzed. Results: A large percentage (40.4%) of young Black adults had more than three risk factors for CHD. In general, they had poor diet score (20.5%), watched television often/very often (49.8%), smoked cigarettes (3.8%), were obese (16.0%), had elevated DBP/SBP (27.3% & 17.7%), FBG (6.4%), TC (31.1%), LDL (29.2%), low HDL (21.7%) and elevated hs‐CRP (15.6%). More males (45.1%) than females (35.7%) had more than 3 risk factors for CHD. Males compared to females had significantly (p<0.05) poorer diet score values (%) (32.6 vs. 8.3), were obese (19.8 vs. 12.2), had higher DBP (35.2 vs. 19.4), SBP (22.0 vs. 13.3) and low HDL (35.2 vs. 8.2). Males also, watched more television (%) (52.7 vs. 46.9), smoked more cigarettes (4.4 vs. 3.1), and had higher FBG (6.6 vs. 6.1) and LDL (30.8 vs. 27.6), whereas, women had higher TC (%) (34.7 vs. 27.5) and hs‐CRP (16.3 vs. 14.8) levels. We demonstrated that risk factors for CHD are found in a large percentage of young Black individuals in South Florida. Interventions to prevent disease must be culturally sensitive for these young adults.
High opinions of fruits and vegetables (F&V) are associated with lower risk of overweight in African American children
Authors: Lakkakula Anantha P , Zanovec Michael , Murphy Ellen P , Tuuri Georgianna
Published: June 2021

The health benefits of fruit and vegetable consumption are well established and the Dietary Guidelines for Americans 2005 recommends sufficient intake of these foods to prevent childhood overweight. Our objective was to examine the relationship between African American children's opinions of F&V and their BMI‐for‐age percentiles. 341 4th and 5th grade children (43% boys; 68% 4th graders) attending low‐income, public elementary schools in southeastern Louisiana participated. Children were measured for height and weight and completed a survey which sought their opinions of 38 different F&V. There was a preference for fruits over vegetables and a negative association between mean F&V opinion score and BMI‐for‐age percentile (r = ‐0.26, p = 0.01). Students were placed in 4 groups based upon F&V opinion scores: very low (1‐1.5), low (1.6‐2.0), moderate (2.1‐ 2.5) and high (2.6‐3.0). Students with very low opinions of F&V were 5.5 times more likely to be at risk of overweight or overweight compared to those with high opinions (OR= 5.5, 95% CI = 1.97, 15.44; p< 0.01). Food preferences are established early in life, therefore nutritionists and other health care professionals should promote children's acceptance and intake of F&V as a measure to reduce the prevalence of overweight among children.

Grant Funding Source: Blue Cross Blue Shield of Louisiana Foundation and LSU AgCenter
Ferroportin Modulates Macrophage‐Mediated Immune Responses
Authors: Johnson Erin E. , Murray Megan , Wessling‐Resnick Marianne
Published: June 2021

The iron exporter ferroportin (FPN) plays a key role in iron homeostasis. Infection and inflammation down‐regulate FPN to limit iron efflux from macrophages. Whether FPN contributes to other macrophage immune responses is unknown. In particular, the intersection of iron metabolism and nitric oxide (NO) production by macrophage inducible nitric oxide synthase (iNOS) has been the subject of much debate. Induction of NO synthesis by macrophage iNOS is a key inflammatory response mechanism triggered by cytokines such as INF‐γ, TNF‐α, and IL‐1 and microbial lipopolysaccharide (LPS). While heme iron is required for iNOS dimerization, it remains unclear whether iron increases or decreases NO production. J774 murine macrophages over‐expressing FPN were used to investigate the influence of iron efflux on iNOS activity. When challenged with LPS or Mycobacterium tuberculosis (Mtb), control J774 cells increase NO synthesis as measured by the Greiss reaction. J774 cells over‐expressing FPN have significantly impaired NO induction in response to LPS or Mtb. Western blot analysis shows that increased NO synthesis in control J774 cells is accompanied by increased iNOS expression, but that upregulation of iNOS protein is markedly reduced when J744 cells over‐expressing FPN are challenged with LPS or Mtb. These results suggest that iron efflux by FPN can limit macrophage‐mediated immune responses.
Soy Sauce Fortified With Nafe‐EDTA Significantly Improves Iron Status for the Middle‐Aged and the Aged
Authors: Wang Sishun , Zhao Xian‐eng , Lu Qiliang
Published: June 2021

Objective: To evaluate the effectiveness of anemia prevention through NaFe‐EDTA Fortified soy sauce for the middle‐aged and the aged. Method: Through a random double blind case‐control study, 365 subjects were selected with 193 exposure cases and 172 controls. Fortified soy sauce and unfortified plain control soy sauce were given to the exposure and control groups, respectively, for six months. Hemoglobin (Hb) level and incidence of anemia was used as outcome indicators. Results: The Hb level in intervention group (both female and male) increased remarkably (P<0.001). The Hb net value increased in intervention group was significantly higher than that in control group. The incidence of anemia declined remarkably after the intervention (P<0.01). Conclusion: Supplementation with NaFe‐EDTA fortified soy sauce effectively reduced the incidence of anemia, and is a effective method to prevent anemia for the middle‐aged and the aged adults in China.
Dietary iron deficiency in strain 40 BXD mice causes diurnal‐dependent alterations in brain iron and activity
Authors: Unger Erica Lynn , Konrad Denise M , Bianco Laura E , Jones Byron C , Beard John L
Published: June 2021

There is an existent literature on Restless Legs Syndrome that supports a role for regional brain iron, dopamine and diurnal cycle variations in its pathophysiology. In this study, Strain 40 of the BXD/Ty RI panel was utilized based on its mid‐range ventral midbrain iron levels among 30 BXD/Ty RI strains initially analyzed. Mice were challenged with control or iron restricted diets from postnatal day 21 to 120 and then brain iron, striatal extracellular dopamine, home‐cage locomotor activity and body temperature were assessed across the diurnal cycle. At day 120, mice fed an iron deficient (ID) diet showed reduced hemoglobin, hematocrit and spleen and liver iron compared to controls. Male and female ID mice displayed diurnal dependent decreases in ventral midbrain iron, while in nucleus accumbens, iron content was reduced only in male ID mice. Diurnal monitoring of home cage activity and body temperature revealed that iron deficiency alters the number and duration of activity cycles in the four hours surrounding the light transitions. During these transition periods, activity increased and decreased at a similar rate as extracellular dopamine and body temperature in control mice and ID females, while these transitions were blunted in ID males. These results suggest that dietary iron deficiency in BXD Strain 40 mice produces diurnal‐dependent alterations in brain iron in dopaminergic regions and in activity patterns.
Impact of Se‐glutathione peroxidase‐1 (GPX1) null on liver and plasma lipid profiles of male mice fed two dietary levels of fat
Authors: Wang Shikui , Lei Xin Gen
Published: June 2021

We previously observed a moderate effect of GPX1 null (GPX1−/−) on plasma lipid profile in young adult female mice fed a high fat diet. The objective of the present study was to assess that effect of GPX1 null in weanling (3‐wk old) male mice. In Exp. 1, 8 GPX1−/− and 8 wild‐type (WT) mice were fed a Torula‐yeast‐sucrose based diet (0.4 mg Se/kg) for 6 wk and killed to assay for concentrations of total cholesterol, total triglycerides, and total non‐esterified fatty acids (NEFA). Compared with the WT, GPX1−/− mice had 33 and 14% lower (P < 0.05) NEFA concentrations in plasma and liver, respectively. The GPX1−/− mice also showed 21% lower (P < 0.05) hepatic total cholesterol concentration than the WT. In Exp. 2, littermates of GPX1−/−, GPX1+/−, and WT (n = 6 per genotype) were fed a high fat diet (28% coconut butter, 58% calories from fat) for 6 wk. Plasma concentrations of total cholesterol, total triglycerides, and NEFA were similar among the three genotypes at the end of the trial. Concentrations of these three measures in liver were 9 to 13% lower in the GPX1−/− mice than the WT, but the differences were not statistically significant. In summary, impacts of GPX1 null on lipid profiles of young male mice were also moderate and seemed to vary with dietary fat intake (NIH DK 53018 TO XGL).
Caffeine Intake and Plasma Zinc Levels among HIV+ Adult Drug Users in Miami
Authors: Campa Adriana , Le Katherine , Rafie Carlin , Sales Sabrina , Baum Marianna K.
Published: June 2021

Objective

Plasma zinc deficiency, the most common nutrient deficiency in HIV, is linked to disease progression. This study investigated the relationship between caffeine intake and plasma zinc levels of HIV+ drug users.

Methods

Informed consent, medical history, physical examination, viral load and dietary intakes were collected. 24‐hour recalls were analyzed using Nutritionist IV Diet Analysis program.

Results

Of the 225 participants, 78% were African American, 62% received ART, and 72% were men. The mean age was 42.6±7.0. The mean caffeine intake was 115 mg. Plasma zinc was inversely correlated with caffeine intake (r = −0.146, p = <0.036). Participants who did not consume caffeine had significantly higher plasma zinc levels compared to those who consumed caffeine (0.673±0.143 μg/ml vs. 0.628±0.125 μg/ml, p = 0.017). Plasma zinc was also higher in participants whose caffeine intakes were below the median (25 mg) compared to those above the median (0.666±0.141 μg/ml vs. 0.630±0.126 μg/ml, p = 0.059). After controlling for age, gender, CD4 count, viral load and ART, caffeine remained significantly associated with plasma zinc, p = 0.0131.

Conclusions

Caffeine intake during the previous 24 hours was associated with decreased plasma zinc levels. Further research is needed to determine the role of caffeine in affecting plasma zinc levels of HIV+ drug users.

Support: Funded by NIDA
Caveolae play a role in EGCG‐mediated protection against linoleic acid‐induced endothelial cell activation
Authors: Zheng Yuanyuan , Lim Eum Jin , Toborek Michal , Hennig Bernhard
Published: June 2021

Flavonoids can protect against inflammatory diseases such as atherosclerosis by decreasing vascular endothelial cell activation. Plasma microdomains called caveolae are particularly abundant in endothelial cells and play a major role in endothelial trafficking and the regulation of signaling pathways associated with the pathology of vascular diseases. We hypothesize that flavonoids down‐regulate inflammatory parameters by modulating caveolae‐regulated cell signaling. We focused on the role of caveolae and its major protein, caveolin‐1, in mechanisms of linoleic acid‐induced endothelial cell activation and protection by the green tea epigallocatechin gallate (EGCG). Pretreatment with EGCG blocked fatty acid‐induced caveolin‐1, MCP‐1 and COX‐2 expression. Similar results were observed with NF‐kappaB DNA binding activity. Caveolin‐1 silencing blocked linoleic acid‐induced expression of MCP‐1 and COX‐2. Exposure to linoleic acid rapidly increased phosphorylation of several kinases, including p38 MAPK, ERK, and Akt. Inhibitors of ERK and Akt down‐regulated the linoleic acid‐induced increase in COX‐2 protein expression. Our data provide evidence that caveolae may play a critical role in regulating vascular endothelial cell activation and protection by flavonoids such as EGCG. (Supported in part by grants from NIH/NIEHS [P42ES07380] and the University of Kentucky AES.)
Individual and additive effects of high protein and resistant starch
Authors: McCutcheon Kathleen Lee , Martin Roy J , Tulley Richard T , Keenan Michael J
Published: June 2021

Multiple mechanisms of food intake control are impacted by diet content and quality. Hormones released by endocrine cells of the GI tract are involved in local and systematic regulation of metabolism (energy regulation, satiety) or disease (predisposition, prevention, treatment). Dietary resistant starch affects satiety and reduces body fat through multiple gut peptide signals. High protein diets also affect satiety and reduce body fat. In this study, we show that adding resistant starch to a high protein diet can enhance this effect. Rats were assigned to 1 of 4 diet groups matched for energy (3.4 kcal/g): LP (15% protein), LPR (15% protein, 20% resistant starch), HP (40% protein), and HPR (40% protein, 20% resistant starch). Data comparisons were significant at p < 0.05. There was lower food intake (LPR, HPR< LP, HP), body fat (HP, LPR, HPR< LP), pH (LPR, HPR< LP, HP), triglycerides (HP, LPR, HPR< LP), and higher GLP‐1 (LPR, HPR> LP,HP). These data support an additive effect for resistant starch and high protein as the levels were significantly lowest in HPR for perirenal fat (p<0.04) and triglycerides (p<0.03). It is proposed that the additive effects of these two dietary components are caused by different mechanisms. High protein diets act to lower body fat through suppression of food intake whereas resistant starch acts to reduce body fat by increasing energy expenditure. Supported by the LSU AgCenter.
Agostach rugosa essential oils reduced plasma triglyceride and cholesterol levels in mice fed normal and high fat diet and suppressed 3‐hydroxy‐3‐methyl‐glutaryl‐Coenzyme a reductase expression in vitro and in vivo
Authors: Chung Mi Ja , Cho Sung‐yun , Lee Sung‐joon
Published: June 2021

Agostach rugosa is a medicinal and ornamental plant in Korea and its essential oils have several bioactive compounds. The HepG2 cells were incubated with 0.1, 0.2, 0.4 and 1 mg/mL of Agostach rugosa essential oils (AREO) for 24 hrs. The mRNA and protein expressions were assessed by RT‐PCR and western blot analysis, respectively. At 1 mg/ml AREO treatment, the levels of the HMG‐CoA reductase mRNA and protein were significantly reduced, whereas the LDL receptor mRNA and protein levels were induced. Next, mice (C57BL/6CrSLC), either on chow or high fat diet, were orally administered with AREO for 6 weeks. In chow fed mice, plasma triglyceride and cholesterol levels were significantly decreased in AREO fed group. The plasma triglyceride levels were also significantly lowered in the AREO fed group compared with controls under high fat diet. The hepatic HMG‐CoA reductase mRNA and protein levels were significantly lowered in the AREO group after 6‐week feeding. These suggest that the AREO may be hypolipidemic by reducing the expression of HMG‐CoA reductase.
Strawberry modulates inflammatory markers and insulin response to high fat meal in overweight men and women
Authors: Ellis Collin , Cheema Mandeep , Linares Amanda , Hyson Dianne , Kappagoda Tissa , Burton‐Freeman Britt
Published: June 2021

Overweight (OW) people are at risk for metabolic syndrome which is associated with elevated inflammatory markers and insulin resistance. Strawberries have a varied phenolic composition with potential for modulating inflammatory status and insulin signaling. Fat intake exacerbates inflammation and insulin resistance. We hypothesized that strawberry would reduce the postprandial inflammatory and insulin response to a high fat meal (HFM). In a randomized, double‐blind, placebo‐controlled, 12‐wk cross‐over trial with a 10 d run‐in, OW men and women (n=24) consumed either a strawberry (Str) or placebo (Pbo) beverage matched in energy and macronutrient composition for 6 wks. At defined intervals for 6 h, hsCRP, adipo‐cytokines, insulin and glucose were measured before and after HFM challenge with Str or Pbo during run‐in (i.e. low Str intake) and again after 6 wks of daily Str or Pbo consumption. During run‐in, the single Str exposure significantly reduced hsCRP (Str, 2.8 mg/L ± 0.1 and Pbo, 3.3 mg/L ± 0.1, p<0.05) and insulin (p=0.002). After 6 wks Str or Pbo and HFM re‐challenge, hsCRP was marginally lower after Str (Str, 2.9 mg/L ± 0.2 and Pbo, 3.3 mg/L ± 0.2, p=0.13) and insulin concentrations tended to be lower. Glucose concentrations did not differ by treatment. These results support the importance of consuming strawberry and other foods rich in bioactive compounds to promote health and reduce chronic disease risk.
Reduction of Cardiovascular Risk Factors in Subjects with Type 2 Diabetes by Pycnogenol® Supplementation
Authors: Zibadi Sherma , Rohdewald Peter J. , Park Danna , Watson Ronald Ross
Published: June 2021

The purpose of this study was to evaluate the clinical effectiveness of Pycnogenol® (Pyc) in reducing use of antihypertensive medicines and cardiovascular disease (CVD) risk factors in subjects with hypertension and type 2 diabetes. In a randomized, placebo controlled trial, 48 individuals, aged 40–75 yrs, with type 2 diabetes and being treated for hypertension with ACE‐inhibitors, were randomly assigned to receive either Pyc pill (125 mg daily) or matched placebo. Pycnogenol® treatment achieved blood pressure control in 58.3% of subjects at the end of the 12 weeks with 50% reduction in individual pretrial dose of ACE‐inhibitors (P < 0.05). Plasma endothelin‐1 decreased 3.9 pg/mL in Pyc‐treated group versus 0.5 pg/mL increase in control group (P < 0.001). Mean HbA1c dropped from 7.9 to 7.1% in Pyc group (P < 0.05), while the control group decreased from 8.1 to 8.0%. Serum fasting glucose level declined by 23.7 mg/dL in Pyc group versus 5.7 mg/dL in control group (P < 0.0001). LDL‐cholesterol improved significantly in Pyc group, declining by 12.7 mg/dL (P < 0.001). A significant decrease in urinary albumin level was observed at week 8 compared to the control group (P <0.05). However this reduction was not significant at 12th week. In summary after 12 weeks of supplementation, Pycnogenol® resulted in improved diabetes control, lowered CVD risk factors, and reduced antihypertensive medicine use versus controls.
Beneficial effect of Pracparatum mungo on change liver enzyme profile and liver protection in Balb/c mice
Authors: Huang Hui‐Yu , Chu Hui‐Chin , Wang Yu‐Chun , Hsieh Yu‐Ting , Tso Tim K.
Published: June 2021

Pracparatum mungo is a typical functional food for Chinese. First, Green bean was manufactured through natural fermentation, then soaking in aqueous Chinese herbal medicine mixture, finally dry by room temperature process to become the refining of natural functional food as Pracparatum mungo. Pracparatum mungo used to use as a traditional medicinal food for liver protection and detoxification in China. The aim of this study was to investigate the histological and biochemical changes in liver of balb/c mice after oral administration Pracparatum mungo. For this purpose, 30male balb/c mice were divided into three groups. Group A only received vehicle and normal chow diet. Group B, C received 25mg/day and 50mg/day Pracparatum mungo with normal diet, respectively. Animal were scarified after 4 weeks, liver tissue and blood sample were obtained. The liver tissue specimens were examined under microscope. The level of ALT, AST, SOD, Caltase, GPX, and GST were determined from serum. The levels of catalase, SOD, GPx, GST activity were significantly increase in Group C. Light microscopic examination of liver specimens reveled normal in all groups. In conclusion, oral administration Pracparatum mungo may enhance liver protection ability to against stress cause liver damage.
Brewing and quality characteristics of Korean traditional grape wine
Authors: Jung Soon Teck , park Yang Kyun , Kang Seong Gook , Ma Seung Jin , Jo Kwang Ho , Yang Eun Jung
Published: June 2021

In Korea, there have been many types of traditional grape wine from seven hundred years ago. And the kind of horse‐blossom‐like‐grape was mainly cultivated. The characteristic on manufacture of Korean traditional wine(KTN) was unique method that grape must adding rice was fermented by nuruk as a starter for brewing. But KTN making became discontinuation on 20th century, and restoration of Korean wine culture is need. The KTN made from grape must added rice by nuruk with three traditional methods, and it's quality was compared to commercial wine made from grape only. Ethyl alcohol contents, acidity, pH, aminoacidity, and total phenolic compounds of three KTNs were 9.2 ∼ 11.2%, 0.9249 ∼ 1.2871%, 3.02 ∼ 3.48, 0,08 ∼ 0.75, and 641.2 ∼ 980.6 mg/100mL, respectively. The result showed higher value in acidity than those of commercial grape wine. Sensory quality properties in color, flavour, taste and overall, of KTNs were no difference from commercial dry wine. Superoxide radical scavenging effect of KTNs were 56.1 ∼ 69.2%, respectively.
Papillary tumor of the spinal cord. Report of two cases
Authors: Mobley Bret , Vogel Hannes
Published: June 2021

Tumors perhaps related to ependymoma include astroblastoma and papillary tumor of the pineal region (PTPR). We report two cases of spinal tumors with similar distinctive features. A 14‐year‐old female had a thoracic tumor in 2001, a lumbar recurrence in 2004, 2 cerebellar lesions in 2006, and in the temporal lobe in 2007, all with identical histology. A 22‐year‐old male presented at age 17 in 1999 with a cervical spine intramedullary tumor that recurred in 2002, 2005, and 2007. A 4th ventricular mass was identified in 2003. The 2003, 2005, and 2007 specimens showed similar histologic features. The tumors showed variable gadolinium enhancement by MRI. Microscopy showed papillary and solid cytoarchitecture with monomorphous epithelioid cells arranged around vascular papillae. IHC revealed: focal GFAP positivity in the 1st case and absence in the 2nd; strong diffuse cytoplasmic EMA positivity; and diffuse cytokeratin AE1/CAM5.2 expression. EM of the 2nd case demonstrated cytoplasmic lumina lined by microvilli, cilia at extracellular surfaces, tight junctions, and absence of interdigitating cell processes. These tumors may be most closely related to ependymomas, but share similarities with the PTPR, and may therefore represent a comparable entity of the spinal cord with a predilection for local recurrence or remote spread within the CNS.
SOX2: A Glioma‐Specific Marker and a Potential Target for Therapy
Authors: Eschbacher Jennifer Mary , Yeh Ru‐Fang , Smirnov Ivan , Feuerstein Burt , Coons Stephen
Published: June 2021

Background: The Central Brain Tumor Registry of the United States reports that gliomas account for 78% of malignant brain tumors. (CBTRUS, 2006. Gliomas are currently diagnosed by histopathologic features. We have identified a transcription factor, SOX2, which appears to be a sensitive and specific marker of gliomas. This transcription factor functions to maintain pluripotency in the stem cell of the developing embryo and is expressed during neurogenesis in the adult human CNS. Design: We analyzed 120 glial tumors and 60 non‐glial primary CNS tumors by immunohistochemistry for expression of SOX2 protein. We also evaluated expression array data for SOX2 in 181 separate glioblastomas. Results: SOX2 expression (>75% malignant cells) was found in 105/120 gliomas, including astrocytomas (WHO grades 1–4), oligodendrogliomas (WHO grade 2, 3), ependymomas (WHO grades 1–3) and oligoastrocytomas (WHO grade 2). Of 60 non‐glial primary CNS tumors, 56 were nonreactive (<10% cells) for SOX2, including 40/44 tumors with neuronal features. Our expression array data showed strong SOX2 expression in 156/181 glioblastomas. Conclusion: Our preliminary data suggest that SOX2 is expressed in the great majority of gliomas but only rarely in neuronal tumors. The fact that SOX2 is believed to regulate stem cell self‐renewal suggests that inhibiting its function may have a therapeutic effect in gliomas.

*This research was funded by Barrow Neurological Institute
Unusual cerebellopontine angle (CPA) tumors: report of three cases
Authors: Kozarski Tzvetan Borissov , Rao Chandrakant
Published: June 2021

CPA tumors have origins from various tissue types present in the area. Schwannoma (75%), meningioma (13%) and epidermoid cyst (5%) are the most common tumors.

Reflecting the anatomic diversity, many uncommon tumors are reported in this location and we present three such cases.

A 51‐year‐old woman presented with difficulty swallowing and unilateral hearing deficit. The tumor extended from petrous bone into the CPA and was diagnosed as myxoid chondrosarcoma. Chondrosarcomas account for 0.048% of intracranial tumors, 37% occurring in the CPA and 8–12% being myxoid type.

A 37‐year‐old woman presented with unilateral hearing loss. An irregular mass destroying left petrous bone and extending into the CPA revealed to be a papillary tumor with blood filled spaces lined by cuboidal epithelium characteristic of endolymphatic sac tumor (EST). No stigmata of von Hippel‐Lindau syndrome were present. EST commonly enters the differential diagnosis of CPA tumors and can mimic choroid plexus papilloma or vascular malformation.

A 65‐year‐old woman presented with severe headache and dizziness. A large mass destroying the temporal bone and extending into the CPA showed classical cribriform pattern of adenoid cystic carcinoma (ACC) focally and solid pattern diffusely. Intracranial ACC is an uncommon tumor, 5–7% occurring in CPA either from a direct extension, or perineural extension or heterotopic salivary gland tissue.
Comparison of pre‐clinical pharmacokinetic (PK) and pharmacodynamic (PD) relationships of cannabinoid CB1 receptor antagonists in a drug development program for weight loss (WL) management
Authors: Scott Dennis O , Hadcock John R , Black Shawn C
Published: June 2021

Background: Establishing PK/PD relationships is critical for drug development. The PK/PD relationship for a CB1 receptor antagonist program for WL was assessed.

Methods: An analysis of PK and PD of in‐house CB1 antagonists and SR141716 in rats was performed.

Results: Receptor occupancy, total plasma and brain concentration, and efficacy (% reduction in food intake [FI] in 2 models of feeding behavior and energy expenditure measured by changes in oxygen consumption [VO2]) were determined in rats. There was a common concentration‐effect relationship across compounds for unbound brain, but not plasma concentrations (Fig 1), that was maintained across efficacy models. Predicted human unbound efficacious plasma concentrations are presented in Table 1.

Conclusions: These studies demonstrate that the novel and highly selective CB1 receptor antagonists CP‐945,598, CE‐178,253, and PF‐431,499 will increase our understanding of the role of CB1 receptor antagonism in metabolic disease.
Comparison of the antinociceptive effects of two pharmacological gases, nitrous oxide (N2O) and hyperbaric oxygen (HBO2)
Authors: Zylstra Carlyn C , Ohgami Yusuke , Chung Eunhee , Shirachi Donald Y , Quock Raymond M
Published: June 2021

HBO2 treatment is reportedly effective in alleviating various chronic pain conditions (Yildiz et al., Curr. Pain Headache Rep. 10:95–100, 2006). To investigate the mechanism of action, male NIH Swiss mice (20–30 g) were exposed to HBO2 (100% O2 @ 2.5 ATA) and assessed for antinociceptive responsiveness using the glacial acetic acid abdominal constriction test conducted in a small animal hyperbaric chamber. This 10‐min exposure evoked a robust antinociceptive effect during the HBO2 exposure. The magnitude of the HBO2‐induced antinociceptive was significantly reduced by pretreatment with naloxone and L‐NAME and partly antagonized by pretreatment with an antiserum against rat dynorphin. By comparison, the magnitude of antinociceptive effect of 70% N2O was significantly attenuated by pretreatment with naloxone, L‐NAME and dynorphin antiserum. These results indicate that HBO2–induced antinociception has commonalities with N2O. HBO2, similar to N2O, seems to evoke an NO‐dependent, opioid receptor‐mediated antinociceptive effect that may involve a different endogenous opioid peptide. (Supported in part by NIH Grant GM‐77153, ASPET SURF Program and the Chico Hyperbaric Center).
Human hepatic and extrahepatic UDP‐glucuronosyltransferase (UGTs) enzymes involved in the metabolism of cannabinoids
Authors: Radominska‐Pandya Anna , Mazur Anna , Lichti Cheryl F. , Gallus‐Zawada Anna , Zielinska Agnieszka K. , Bratton Stacie M. , Moran Jeffery H.
Published: June 2021

Δ9‐Tetrahydrocannabinol (Δ9‐THC) is the primary psychoactive compound found in cannabis plants which invoke physiological responses via cannabinoid CB1 receptors. THC derivatives are known to be the subject of cytochrome P450 (P450) and UDP‐glucuronosyltransferases (UGTs) metabolism. Despite ample P450 characterization data, there remain gaps in our understanding of human phase II enzymes responsible for THC derivative metabolism and excretion. The activities of 12 human recombinant UGTs towards several THC derivatives, cannabinol (CBN), cannabidiol (CBD), (−) ‐Δ8‐THC, (−) ‐Δ9‐THC, (±)‐11‐hydroxy‐Δ9‐THC (11‐OH‐THC), and (−)‐11‐nor‐9‐carboxy‐Δ9‐THC (COOH‐THC), have been investigated in this study. C14‐labeling assays and HPLC‐MS/MS product confirmations show that UGT1A1, −1A3, −1A8, −1A9, −1A10, and −2B7 are involved in the glucuronidation of CBN, CBD, 11‐OH‐THC, and COOH‐THC. CBN and 11‐OH‐THC are primarily metabolized by an extrahepatic isoform, UGT1A10, with apparent Km values of 55 and 16 μM, respectively. COOH‐THC is a substrate for 2 hepatic UGTs, −1A1 and −1A3. All of the tested enzymes show little to no activity with (−) ‐Δ8‐THC and (−)‐Δ9‐THC. This is the first demonstration that cannabinoids are glucuronidated by specific human recombinant UGTs, with UGT1A10 and 1A3 being the major isoforms involved. (NIH‐DK60109 and GM075893 to AR‐P; U90/CCU616974‐07 to JM)
Behavioral Evaluation of acupuncture treatment in AMPH experimental administration ‐ Preliminary Results
Authors: Souza Ivone Antonia , Nolasco Varão , Rafael Ana Isabel , Farinha Rodrigo , Cabrita António Silvério
Published: June 2021

This study was designed to evaluate the impact of acupuncture treatment of behavioral changes caused by amphetamines (AMPH).

12 female Wistar rats were randomly divided in 3 groups, all treated with 3mg of AMPH by subc. inj. Group I was kept in observation. Group II was submitted to the application of acupuncture needles 15 minutes after AMPH, at the following points: LV13; SP2; SP6; SP9; ST36; UB20 and Ren Mai 12. Group III was submitted to acupuncture needles application in Sham points. Locomotor behavior was assessed using the open field test. Group III submitted to the application of the needles in sham points

The animals of group I showed lateral and back movements, jumps, excessive around movements, clonic, tonic and general convulsions, aggressiveness to environment, low position of the posterior and anterior members, pallor of the eyes, ears and feet; total absence of diuresis and defecation; lost of space perception, and abdominal distension. The animals of group II showed respiratory frequency diminishing, recovery from pailure, keeping of active reflex to stimuli. These animals didn't show any convulsion. The application in Sham points does not reproduce the benefits of using the accurate acupuncture points.

These results that the animals submitted AMPH administration show locomotor and behavior changes that become reduced by the application of needles in the acupoints
Rapid substrate‐induced down‐regulation of rat dopamine transporter function in vitro: dorsal striatum vs. nucleus accumbens
Authors: Richards Toni L. , Yamamoto Dorothy J. , Zahniser Nancy R.
Published: June 2021

Dopamine (DA), d‐amphetamine (AMPH) and methamphetamine (METH) are DA transporter (DAT) substrates that also rapidly and transiently reduce cell surface expression of DATs in dorsal striatum (dSTR) and cells expressing cloned DATs. However, it is not clear if DATs are regulated similarly by substrates in nucleus accumbens (NAc). Here, we investigated whether brief in vitro exposure to DAT substrates differentially regulates DATs in synaptosomes prepared from dSTR or NAc of male Sprague Dawley rats. Synaptosomes were pre‐incubated with DA, AMPH, METH (3–30 μM) or buffer for 5–30 min at 37oC and washed twice at 4oC; specific uptake of 0.5 nM [3H]DA, defined with 100 μM cocaine, was measured for 3 min at 37oC. As expected, [3H]DA uptake was 54% lower in NAc than in dSTR, and substrate pre‐incubation significantly reduced [3H]DA uptake in dSTR in a time‐ and concentration‐dependent manner. Although in NAc [3H]DA uptake was also reduced by pre‐incubation with DA, AMPH or METH, statistical significance was not reached with any pre‐incubation time or concentration. Kinetic analyses after a 15 min pre‐incubation with 10 μM AMPH confirmed a lower maximal DAT velocity in dSTR, but not in NAc. Our results suggest that brief substrate exposure more efficaciously down‐regulates DATs in dSTR; however, surface biotinylation experiments are needed to confirm these observations. Supported by DA004216, DA014204, AA007464, DA015050.
The research on the effects of APS increased insulin sensitivity and reduced ER stress in a STZ induced rat model of type 2 diabetes
Authors: Wang Nian , Ouyang Jingping , Zou Feng , Zhang Deling , Wu Dehong
Published: June 2021

Recent researches have identified that endoplasmic reticulum stress (ERS) is involved in the development of type 2 diabetes. Astragalus polysaccharide (APS) is extracted from Astragalus membranaceus (Huangqi) and has the potential as a immunomodulator with wide clinical applications. Our research is to investigate the effects of APS on ERS and insulin sensitivity in a rat model of type 2 diabetes. We established animal models of type 2 diabetes by high fat forage associated with small dosage of STZ(25mg/kg) injection through abdominal cavity and randomly divided animals into four groups: diabetes group(DM group), diabetes+APS group(DA group, control group(C group), control+APS group(CA group). CA group and DA group were administered with APS(700mg/kg/day) while the other two groups were administered with the same dose of sodium chloride for 8 weeks. We found that the FBG and RBG of DA group were markedly lower than those of DM group, the index for each time point of oral glucose tolerance test were increased than those of the DM group(p<0.01). The expression of PTP1B, p‐IRE‐1 were significantly increased in DM group to compare with C group(p<0.01), but the expression in DA group was decreased than DM group(p<0.05). The expression of uncleaved ATF6 in DM group was lower than C group, but it increased after treatment with APS(p<0.01). These results indicate that treatment with APS can lower the level of blood glucose and increase insulin sensitivity probably through decreasing the level of expression of PTP1B, and APS can relieve ERS through reducing the expression of activated ATF6 and phosphorylated IRE‐1, the relief of ERS by APS was also probably one of the mechanisms of its effects on enhancement of insulin sensitivity.

(This research is supported by national science foundation of China granted NO: 30771023)
Progesterone metabolite allopregnanolone attenuates the reinstatement of cocaine‐seeking behavior in female not male rats
Authors: Anker Justin Jack , Holtz Nathan Alexander , Pawlik Jennifer Lee , Carroll Marilyn E
Published: June 2021

Previous research indicates that progesterone decreased cocaine‐seeking in female rats. The attenuating effects of progesterone may be, in part, due to its metabolite, allopregnanolone (ALLO). ALLO, is a neurosteroid that is also a positive modulator of GABA A receptors. ALLO has been shown to decrease the sensitizing effects of cocaine and reduce lethality associated with cocaine overdose in mice. The purpose of the present study was to examine the effects of ALLO on the reinstatement of cocaine‐seeking in female and male rats. Rats were trained to lever press for i.v. infusions of cocaine during 2‐hour sessions. Once acquisition criteria were met, they continued cocaine self‐administration for 14 days. Cocaine was then replaced with saline, and lever‐pressing was allowed to extinguish over 21 days. After the extinction phase rats received ALLO (15 mg/kg or 30 mg/kg) or vehicle pretreatment 30 min prior to the session for 3 days. Rats were then tested during reinstatement with 3 randomly administered doses of cocaine (5, 10 and 15 mg/kg, i.p.), each separated by one day of saline treatment. The results of the study indicate that ALLO, administered to females at the 15 and 30 mg/kg dose, decreased cocaine‐seeking. However, ALLO did not effect cocaine‐seeking behavior in male rats. These findings suggest that ALLO may provide a novel approach for preventing relapse in female cocaine‐abusers.
Effect of Neurosteroid Withdrawal on Hippocampal GABA‐A Receptor α4‐Subunit Expression in Female Mice
Authors: Zheng Y‐C , Reddy Doodipala
Published: June 2021

Progesterone reduces seizure susceptibility partly through conversion to neurosteroids such as allopregnanolone, which enhances GABA‐A receptor function. In animal models, withdrawal from chronic progesterone and, consequently, of allopregnanolone levels in brain, has been shown to increase seizure susceptibility, which could be highly relevant to catamenial epilepsy in women. The most striking finding following neurosteroid withdrawal is a marked increase in expression of the hippocampal GABA‐A receptor α4 subunit. However, the molecular mechanisms of neurosteroid withdrawal‐induced alterations in α4 subunit expression remain unclear. In this study, we tested the hypothesis that the PR pathway is involved in neurosteroid withdrawal‐induced synaptic plasticity. We tested this hypothesis utilizing the PRKO mouse model. Female mice were treated with progesterone for 7 days and hippocampus mRNA extracted 24 h after finasteride co‐administered with progesterone on day 7. The amount of α4 subunit mRNAs were then determined by TaqMan real‐time RT‐PCR method. Allopregnanolone withdrawal induced a significant increase in the α4 subunit expression in the hippocampus in WT mice. These results confirm that neurosteroid withdrawal is associated with alterations in α4 subunit expression in female adult mice. *Supported by NIH grant NS051398*
NATURAL PRODUCTS CONTAINING IRON INDUCES CELL PROLIFERATION AND INCREASE THE S PHASE OF CELL CYCLE IN VITRO.
Authors: Reyes‐Esparza Jorge , Martinez Manuel Rendon , Gomez Maria Antonieta , Gonzalez Raul , Aznar Elisa , Rodriguez‐Fragoso Lourdes
Published: June 2021

It is estimated that 2 000 millions of persons have deficiency of iron in all world. Anemia due to a deficiency of iron is one of nutritional problems in development countries. Deficiency of iron affect in most importantly to women during menstruation, pregnancy and childbirth. Combifer® and Neotrofin‐C® are two new drug anti‐anemic prepared in Centro Nacional de Biopreparados of la Habana (Cuba). They contain aminoacid, proteins, minerals and iron in ferroused form. The objective of this study was to evaluate the effect of Combifer® and Neotrofin‐C® in a model based in cells and chicken embryos. BMK (renal cells), WRL68 (hepatic cells), and KHOS (bone cells) were cultured in DMEM + 10% FCS+ 4 mM glutamine and antibiotics for 24 h. After time cells were treated with 0.5, 0.75, 1.0, 1.25, 1.5, 1.75 y 2.0 ug/ml, and then the assay of MTT and flow cytometry were made in order to know the effect on viability, proliferation and cell cycle. Our results showed that Neotrofin‐C® and Combifer® did not induce toxic effects on cells by contrast it induced cell proliferation in all cell lines and increased the S phase of cell cycle in WRL68 and BMK cells. Combifer®. Therefore the use of Combifer® and Neotrofin‐C® might to have pharmacological effects on other cells than blood cells.
Angiotensin Type 1 Receptor (AT1R) And Alpha‐1D Adrenoceptor Form A Heterodimer During Pregnancy‐Induced Hypertension
Authors: Lopez Pedro , Gonzalez Ma. Lourdes , Godinez Daniel
Published: June 2021

Pregnancy courses with low vasopressor response to angiotensin II (Ang II) and to adrenergic agonists. In pregnancy‐induced hypertension (PIH), both effects are reverted. It has been reported that Ang II regulates adrenergic system. It is not well known, however, the interactions between receptors from both systems. The aim of this work was to study if AT1R and a1D adrenoceptor heterodimerize during PIH. We used a subrenal aorctic coarctation (SRAC) model in female Wistar rats, measuring blood pressure and proteinuria. Aortic tissue samples were prepared for confocal imaging using fluorescent antibodies against each receptor and a subset were homogenized and incubated with disuccinimidyl tartarate, immunoprecipitated using anti‐a1D adrenoceptor antibody and immunoblotted using an Anti‐AT1R antibody. We found hypertension and proteinuria in SRAC‐pregnant rats, and AT1R‐a1D adrenoceptor heterodimer in both, pregnant non‐SRAC and pregnant SRAC groups. In pregnant non‐SRAC rats, heterodimer is barely detected. In pregnant SRAC rats however, we found higher heterodimerization. These results suggest that AT1R and a1D‐adrenoceptor may form heterodimers, and these heterodimers may play a role in the pathophysiology of pregnancy‐induced hypertension. Supported by CONACYT 46217
Gender is a factor that can impact the severity of doxorubicin (DXR) toxicity in spontaneously hypertensive rats (SHR)
Authors: Herman Eugene , Knapton Alan , Zhang Jun , Hiraragi Hajime , Lipshultz Steven
Published: June 2021

Female pediatric patients appear to be more susceptible to doxorubicin cardiotoxicity than males. The present study sought to determine whether gender affects the severity of DXR‐induced cardiac and non cardiac tissue toxicity. Male and female SHR (14 weeks of age)(15/group) were administered 1 mg/kg DXR (iv) weekly for 9, 10 or 12 weeks. The study was terminated 1 week after the final dose. Four male SHR died after 9 or 10 DXR doses. Weight gain was retarded to a greater extent in DXR‐treated male than female SHR (5% of male control vs 46% of female control). Serum levels of urea nitrogen (BUN) were elevated only in male SHR (↑220–250%).Changes in serum concentration, over pretreatment levels, of cholesterol (↑630–960% vs 200–520% female), triglycerides (↑910–1790% vs 600% female) and albumin (↓75–77% vs 15–50% female) were significantly more profound in the DXR‐treated male SHR. DXR‐induced myocardial alterations were more severe in male (avg lesion score=2.3) compared to female SHR (avg lesion score=1.5)(p<0.01). Serum levels of cardiac troponin T were significantly higher in male (avg 0.62 ng/ml) than female (avg 0.10 ng/ml)(p<0.01). DXR caused more severe renal lesions in male (avg lesion score=3.9) than in female (avg lesion score=2.2) SHR (p<0.01). The findings in adult male SHR imply that gender can play a significant role in the susceptibility of various tissues, such as the heart, to the toxic effects of DXR.
In‐vitro and in‐vivo pharmacology of a novel TRPV1 receptor antagonist: JNJ38748021
Authors: Bhattacharya Anindya , Hawryluk Natalie A , Merit Jeffrey E , Nasser Nadia , Ao Hong , Wang Qi , Tham Chui‐Se , Maher Michael P , Kansagara Mena , Scott Brian P , Hack Michael D , Breitenbucher James G , Chaplan Sandra R , Wickenden Alan D
Published: June 2021

TRPV1 is a polymodal nociceptor that plays a critical role in modulating sensory thresholds and is an attractive target for analgesia and inflammatory disorders. Here we report a novel tetrahydropyrimidoazepine, JNJ38748021 that attenuated capsaicin activation of the recombinant TRPV1 receptor with a pIC50 of 7.2 ± 0.05 against both the rat and the human isoforms (FLIPR). Likewise, JNJ38748021 was also an equipotent antagonist against both pH and anandamide‐induced activation of rat and human TRPV1. The compound also displaced resiniferatoxin in a binding assay with a pKi of 7.2 (rat) and 7.7 (human). Against the native form of TRPV1, JNJ38748021 blocked capsaicin‐induced rat bladder contractility with a pKB of 7.1 (isometric contraction of isolated tissue) and a pIC50 of 6.8 in isolated rat DRG cultured neurons (whole‐cell patch clamp). JNJ38748021 was modestly orally bioavailable (35%) in rats at 10 mg/kg with a Cmax of about 1 μM. The clearance and half‐life of the compound was 2.2 l/hr/kg and 1.43 hr, respectively in rats. In a pharmacodynamic model of capsaicin‐induced hypotension, the plasma concentration for half effect (Cp50) was 1 μM. JNJ38748021 (10 and 30 mg/kg, p.o) was efficacious in reversing carrageen‐induced thermal hyperalgesia in rats. In conclusion, JNJ38748021 is a novel TRPV1 antagonist with analgesic properties.