bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Obsessive-Compulsive Disorder and Psychosis
Authors: Gangdev Prakash S
Published: March 2003

Objective: To report on patients with comorbid Obsessive-Compulsive Disorder (OCD) and a psychotic disorder, and to discuss the relationship between OCD and psychosis.

Method: Case histories of seven patients seen at a rural mental health clinic in New Zealand are presented. Six of them were treated with selective serotonin uptake inhibitors (SSRIs).

Results: Four patients had sexual obsessions and two reported aggressive obsessions. One patient had obsessive doubts and checking compulsions. Six patients improved with the addition of an SSRI to their ongoing neuroleptic medication.

Conclusions: 1) OCD and psychosis may coexist by chance and may be unrelated. 2) An obsession may become a delusion or vice versa. 3) A reactive delusion of guilt or persecution may develop. 4) An obsession may trigger a psychotic episode or vice versa. 5) Obsessions may be misdiagnosed as delusions or hallucinations. 6) Recognition and treatment of OCD may improve the outcome of psychosis.
Early experience in the use of Levovist ultrasound contrast in the evaluation of liver masses
Authors: Plew J , Sanki J , Young N , Gruenewald S , Dwyer R , Brancatisano R
Published: March 2003

The aim of the present paper was to assess the utility of Levovist in defining the pathology of liver masses. Levovist is a new ultrasound contrast agent consisting of galactose microparticles, air bubbles and palmitic acid. Prospective studies were performed in patients referred for further evaluation of known liver masses. Levovist was peripherally injected and colour Doppler ultrasound studies were performed. Findings were correlated with clinicopathology and three other imaging modalities: biphasic spiral CT, CT arterial portography and contrast MRI. Twenty‐five patients were studied (15 male and 10 female) in the age range 25–74 years. Liver masses ranged from 0.5 to 7 cm in maximum diameter. Thirteen lesions were benign and 12 were malignant (four hepatomas (HCC) and eight metastases). Levovist enhancement occurred in 18 lesions. Of these, six were benign (four focal nodular hyperplasias (FNH) and two haemangiomas). All 12 malignant lesions demonstrated enhancement. The HCC showed a mosaic pattern of central and peripheral enhancement, and the FNH demonstrated a spoke‐wheel pattern. It was not possible to distinguish between haemangiomas and malignant lesions. Non‐enhancing lesions may well be benign, with all malignancies showing some enhancement. Characteristic enhancement patterns were found for HCC (mosaic) and FNH (spoke‐wheel). It was not possible to distinguish between metastases and benign lesions (haemangiomas) when the pattern of enhancement was peripheral.
Radiotherapy utilization in New South Wales from 1996 to 1998
Authors: Barton Michael
Published: March 2003

The purpose of the present study was to examine utilization rates of radiotherapy by newly diagnosed cancer patients in New South Wales (NSW) from 1996 to 1998. The 1989 report of the Australian Health Ministers’ Advisory Council (AHMAC) recommended that 50% of all newly diagnosed cancer patients should receive radiotherapy. Previous reports showed that the true rate was between 30 and 36%. In 1991 and 1995 the NSW Department of Health developed strategic plans that were intended to implement the AHMAC recommendation. An analysis was carried out of activity reports of radiation oncology departments in NSW and its component Area Health Services (AHS). All NSW patients newly diagnosed with cancer between 1996 and 1998 and treated by radiotherapy were included in the study. A total of 37% of newly diagnosed cancer patients received radiotherapy in NSW in 1998. This has increased from 30% since 1990–91. Rural AHS in 1998 had an identical average rate of 37% (range: 23–54%) when compared to urban AHS (average: 37%; range: 26–49%). Rural AHS have increased utilization from 19% in 1990–91. Area health services with a radiation oncology department had a slightly higher rate of utilization than those AHS without a radiation oncology department (39 and 36%, respectively). The rates of utilization of radiotherapy in NSW in 1998 continued to be well below the benchmark set by AHMAC and varied widely between AHS. Attention to and expansion of services should be focused on both rural and urban areas of need.
Diastrophic dysplasia with severe primary kyphosis and ‘monkey wrench’ appearance of the femora
Authors: Bieganski Tadeusz , Faflik Jakub , Kozlowski Kazimierz
Published: March 2003

The cases of two sisters with severe diastrophic dysplasia who showed some unusual radiographic features (kyphosis secondary to hypoplasia/dysplasia of the lumbar spine and a ‘monkey wrench’ appearance of the proximal femur) are reported here. Absent patellae were another feature that has not previously been reported in diastrophic dysplasia.
Pigmented villonodular synovitis: Magnetic resonance features of an unusual case of bilateral hip joint involvement
Authors: Patkar Deepak , Prasad Srinivasa , Shah Jeshil , Patankar Tufail , Kothari Suren
Published: March 2003

Pigmented villonodular synovitis (PVNS) is usually a mono‐articular disorder. Bilateral symmetrical affection of this disease process is exceptional. A case is reported of a patient with PVNS with bilateral, symmetrical hip joint involvement.
Dual phase 99m‐technetium Sestamibi imaging with single photon emission computed tomography in primary hyperparathyroidism: Influence on surgery
Authors: Nordin A Jalil , Larcos George , Ung Owen
Published: March 2003

The purposes of this study were to determine the positive and negative predictive values of 99m Technetium (99mTc) Sestamibi dual phase imaging with single photon emission computed tomography (SPECT) for parathyroid adenomata or hyperplasia and the effect of preoperative localization on duration of surgery. We reviewed 33 adults (14 men, 19 women; mean age 53 years) with newly diagnosed primary hyperparathyroidism who underwent neck exploration. The duration of surgery for this cohort was compared with a group of historical controls (n = 53) who underwent surgery without preoperative SPECT. At surgery, there were 21 adenomata (including one carcinoma), 10 patients with hyperplasia and two with no pathology detected. The positive predictive values (PPV) for adenomata and hyperplasia were 95% and 100%, respectively. The negative predictive values (NPV) for these entities were 67% and 22%, respectively. The mean weight of adenomata detected was 3.4 g (range 0.2–17 g). Mean duration of surgery was 112.6 min as compared with 113 min in the historical controls (P = not significant). We conclude that 99mTc Sestamibi dual phase imaging with SPECT has an excellent PPV for parathyroid adenomata and hyperplasia, but does not contribute to reduced duration of surgery in patients undergoing neck exploration for the first time. The NPV is low, suggesting that a negative result does not exclude an adenoma or hyperplasia.
Strontium‐89 treatment for prostate cancer bone metastases: Does a prostate‐specific antigen response predict for improved survival?
Authors: Zyskowski Adam , Lamb David , Morum Pauline , Hamilton David , Johnson Carol
Published: March 2003

A review of 50 patients treated with strontium‐89 for prostate cancer bone metastases from January 1993–1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate‐specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium‐89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post‐treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium‐89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.
Emphysematous gastritis: Case report and literature review
Authors: Shipman Peter J , Drury Paul
Published: March 2003

Emphysematous gastritis is a rare form of gastritis that results from infection of the stomach wall by gas‐forming organisms. Diagnosis of this commonly fatal condition rests on radiological demonstration of gas within the stomach wall. This can be observed on plain radiographs or CT scans of the abdomen. Only by prompt diagnosis and treatment can mortality be avoided. A new case of empysematous gastritis, diagnosed on CT scan by the demonstration of both intramural and portal venous gas, is presented and the literature is reviewed.
Hydatid pulmonary emboli
Authors: Smith Gerard J , Irons Steven , Schelleman Anthony
Published: March 2003

A case of secondary hydatosis, initially misdiagnosed as pulmonary metastases, is presented. The dissemination of hydatid cysts within the lungs in this case was the consequence of direct rupture of a hepatic hydatid into the inferior vena cava. A brief overview of the pathophysiology of hydatid disease, including a discussion of the types of hydatid rupture (contained, communicating and direct), is presented.
Orbital multiple myeloma: Case report and review of computed tomography features
Authors: Ajithkumar TV , Sivasankar C , Ramachandran K
Published: March 2003

Orbital involvement at diagnosis in multiple myeloma is rare. Only a few a cases are reported with computed tomographic features. We report a case of orbital myeloma, and relevant medical reviews on computed tomography features are discussed.
Evaluation of the effectiveness of digital radiography in emergency situations
Authors: Pathi R , Langlois S
Published: March 2003

The time differences between digital and conventional radiography for emergency patients were investigated, and clinician satisfaction with the two modalities was compared. Time–motion data was collected daily over 5 weeks for a digital group and a conventional X‐ray group. For standardization purposes, only emergency patients requiring chest X‐rays were selected for the study. Data were collected from 30 patients in each of the two groups in the time–motion study, and 31 out of 50 Emergency and Intensive Care clinicians responded to the questionnaire. Results were analysed by percentage, and χ2 analysis was used where appropriate. The time for availability of images to requesting clinicians was 70% less for digital images compared to conventional radiography. The overall satisfaction between digital and conventional radiography was very similar, but most clinicians expressed an opinion that digital radiography offered significant image modification advantages.
Quality assurance and radiofrequency heating
Authors: Desmond Patricia , Syngeniotis Ari , Fleming Steven , Jackson Graeme
Published: March 2003

This paper proposes an inexpensive means of assessing radiofrequency (RF) power deposition in a magnet. This is particularly important at 3T where sequences approach Food and Drug Administration approved RF limits. It will also be of interest to operators at 1.5 T as part of their ongoing quality assurance programs. At 3T, we found that the RF power deposited in the magnet was less than that read by the MR power monitor.
Petrous apex arachnoid cyst extending into Meckel's cave
Authors: Batra Arun , Tripathi Rajendra Prasad , Singh Anil Kumar , Tatke Medha
Published: March 2003

A rare case of arachnoid cyst involving the petrous apex with an unusual clinical presentation has been described with special emphasis in the imaging features and importance of accurate presurgical diagnosis. Differentiation from the other benign lesions involving the petrous apex and the role of newer MR techniques in the diagnosis of these lesions has been highlighted.
Cervical osteochondroma as a cause of spinal cord compression in a patient with hereditary multiple exostoses: Computed tomography and magnetic resonance imaging findings
Authors: Çirak Bayram , Karabulut Nevzat , Palaoglu Selçuk
Published: March 2003

Spinal cord compression is a rare but extremely serious complication of hereditary multiple exostoses (HME). Imaging of the spine is important for surgical planning and follow up. We present CT and MR findings in a male patient with HME who developed spinal cord compression from a cervical osteochondroma. Complete recovery was achieved following surgery.
Cost‐effectiveness of CT thorax and bronchoscopy in haemoptysis with normal CXR for exclusion of lung cancer
Authors: Law GTS , Wong CY , Chan YC , Shum TT , Lok PS , Wong KY
Published: March 2003

As fibre‐optic bronchoscopy and CT thorax become more widely used, patients with haemoptysis who had normal CXR and sputum results are more commonly offered both CT and bronchoscopy to exclude lung cancer. Doctors who are under possible litigation pressure arising from missed diagnoses of lung cancer are often exhaustive in their investigations, even when the haemoptysis has been transient. The present study aims to investigate the number of cancer patients who can be detected with the two investigations, and compare recent similar study results with archive results. We found that despite the use of more efficient investigation tools, the yield is paradoxically much lower and, hence, less cost‐effective than that of previous studies. The likely reason is that doctors tend to over‐investigate, even for short‐term, minimal blood‐streaked sputum, which is common among simple bronchitis. In order to be more cost‐effective, these investigations should be used more selectively and for high risk patients such as those with prolonged haemoptysis and those who are heavy smokers.
Dose distribution and morbidity after high dose rate brachytherapy for prostate cancer: Influence of V150 and V200 parameters
Authors: Duchesne Gillian M , Das Ram , Toye Warren , See Andrew
Published: March 2003

The purpose of this study is to identify factors predicting morbidity in patients undergoing high dose rate (HDR) brachytherapy boost with external beam irradiation for prostate cancer. Acute and late morbidity data were collected for 104 prostate cancer patients treated with an HDR boost together with external beam radiotherapy. Significant urinary and rectal morbidity were correlated with urethral and rectal point doses, and the proportions of the target volume receiving 100%, 150% and 200% (V200) or more of the prescribed dose. Rectal or urethral point doses did not predict morbidity. By contrast, the V200 was significantly higher for patients experiencing either acute or late urinary morbidity. The cut‐off V200 was 15% of the target volume. Although theoretically beneficial for tumour cell kill, the treatment of significant proportions of the prostate to high dose might be associated with increased morbidity, and should preferably be avoided.
Intracranial Tc99m MDP uptake in Sturge −Weber syndrome
Authors: Hui Cathryn , Lau Kenneth KP
Published: March 2003

A case of intracranial extraosseous 99mTc MDP uptake is presented, which was found on CT to be due to dystrophic gyral calcification characteristic of Sturge−Weber syndrome (SWS). The imaging characteristics of SWS are described. The possibility of extraosseous MDP uptake should be considered when unusual or atypical ‘hot spots’ are seen on bone scanning.
Ca2+‐ACTIVATED K+ CURRENT INDUCED BY EXTERNAL ATP IN PC12 CELLS
Authors: Fujii Fumio , Kimura Junko , Tase Choichiro
Published: March 2003

1. The effect of external ATP on the membrane current was investigated in PC12 cells by whole‐cell voltage‐clamp techniques.

2. Lower concentrations of ATP (1 or 10 μmol/L) induced only an inward current at 1 mmol/L EGTA in the K+ pipette solution, while higher concentrations of ATP (100 μmol/L and 1 mmol/L) induced an outward current following the inward current.

3. Lowering the EGTA concentration in the pipette solution induced a larger outward current following ATP application. The membrane potential at which the outward current crossed with the control before ATP application was more negative at lower concentrations of EGTA in the pipette.

4. The development of the outward current was blocked by a Ca2+‐free external solution, 5 mmol/L tetraethylammonium and a Cs+ pipette solution instead of K+, indicating that the outward current was a Ca2+‐activated K+ current.

5. Charybdotoxin (0.1 μmol/L) and iberiotoxin (0.1 μmol/L), but not apamin (0.2 μmol/L) blocked the development of the outward current, indicating that the ATP‐induced outward current is a BK‐type Ca2+‐activated K+ channel current and not the SK type.

6. UTP had no effect on the membrane current, indicating that the ATP‐induced current change was not mediated by P2u but by P2x purinoceptor.

7. In conclusion, stimulation of P2x purinoceptors by ATP induces a Ca2+‐permeable inward current that results in increases in intracellular Ca2+ concentrations and activation of a BK‐type Ca2+‐activated K+ current in PC12 cells.
RADICAL IDEAS: GENETIC RESPONSES TO OXIDATIVE STRESS
Authors: Demple Bruce
Published: March 2003

1. Complex genetic systems counteract different types of ‘oxidative stress’ caused by reactive derivatives of oxygen.

2. The bacterial oxyR system responds to peroxide stress and is governed by OxyR, a transcription factor activated by the formation of an intramolecular disulphide bond in H2O2‐treated cells. Activated OxyR switches on several genes encoding antioxidant functions, such as catalase. During aerobic growth, oxyR acts homeostatically to regulate cellular H2O2 levels.

3. The bacterial soxRS system responds to superoxide or nitric oxide (NO) stress and is activated in two transcriptional stages. The SoxR protein is activated by oxidation of its [2Fe–2S] centres in cells exposed to superoxide‐generating agents, such as paraquat, or to NO. Activated SoxR stimulates the soxS gene and SoxS protein then induces at least 15 genes encoding antioxidant functions, such as superoxide dismutase, metabolic functions, such as fumarase, and antibiotic resistance by activation of efflux pumps. The soxRS system may function in resistance to NO‐generating immune cells and may contribute to clinical antibiotic resistance.

4. Human cells respond to subtoxic levels of NO by inducing 12 proteins and down‐regulating others. A key induced activity is haem oxygenase 1, which is controlled post‐transcriptionally.

5. Motor neurons exhibit adaptive resistance to NO, triggered by exposure to subtoxic NO levels, and providing resistance to usually cytotoxic levels of this agent or H2O2. Adaptive resistance to NO depends strongly on the inducible heam oxygenase activity.
SUBLINGUAL NIFEDIPINE IN ELDERLY PATIENTS: EVEN A LOW DOSE INDUCES MYOCARDIAL ISCHAEMIA
Authors: Ishibashi Yutaka , Shimada Toshio , Yoshitomi Hiroyuki , Sano Kazuya , Oyake Nobuyuki , Umeno Tetsuhiro , Sakane Takeshi , Murakami Yo , Morioka Shigefumi
Published: March 2003

1. Low doses of sublingual nifedipine are still used for the treatment of hypertensive crises, although recent studies have raised concerns that sublingual nifedipine may cause serious dose‐dependent adverse effects. The present study was performed to test the safety of low‐dose sublingual nifedipine administered to elderly hypertensive patients.

2. Systemic blood pressure measurements and electrocardiographic (ECG) examinations were performed before and 45–60 min after a 5 mg dose of sublingual nifedipine in 93 consecutive hypertensive patients, 65 years of age or older, who were without coronary artery disease. In 33 patients, the effects of nifedipine on myocardial lactate metabolism were studied during cardiac catheterization.

3. In all patients, following nifedipine administration, blood pressure (BP) decreased significantly, while heart rate (HR) increased, and symptoms associated with elevated BP disappeared. However, changes consistent with myocardial ischaemia appeared on the ECG in six of 55 patients with left ventricular hypertrophy (LVH) and in one of 38 patients without LVH, although only two of these seven patients experienced angina‐like precordial tightness. Sublingual nifedipine decreased myocardial lactate extraction from 52±13 to 38±19% in 20 patients with LVH (P = 0.02), but myocardial lactate extraction remained stable in 13 patients without LVH (49±7 to 50±5%; NS). The change in lactate extraction was significantly correlated with the percentage change in diastolic arterial pressure (r = 0.77, P < 0.001).

4. These results suggest that sublingual nifedipine, even at the low dose of 5 mg, may cause myocardial ischaemia in some elderly patients with LVH that is associated with a marked reduction in coronary perfusion pressure.
Effects Of Diabetes On Non‐Adrenergic, Non‐Cholinergic Relaxation Induced By Gaba And Electrical Stimulation In The Rat Isolated Duodenum
Authors: Kaputlu I•rfan , Özdem Sadi , Şadan Gülay , Gökalp Osman
Published: March 2003

1. The effects of streptozotocin (STZ)‐induced experimental diabetes on nitrergic‐mediated responses to GABA and electrical field stimulation (EFS) have been evaluated in rat isolated duodenum.

2. In the presence of noradrenergic and cholinergic blockade, EFS (60 V, 1 ms, 0.1–32 Hz) induced frequency dependent relaxations of the preparation. GABA also caused submaximal relaxation of the rat duodenum. The relaxations induced by GABA and EFS were reduced in duodenal tissues from diabetic rats compared with control rats.

3. Neither ATP‐ nor sodium nitroprusside‐induced relaxations were altered in diabetic duodenal tissues. GABA‐ and EFS‐induced relaxations were inhibited by NG‐nitro‐
L‐arginine methyl ester (
L‐NAME; 300 mmol/L) in both diabetic and control rats. Although the inhibition caused by
L‐NAME of GABA‐ and EFS‐induced relaxation was partially reversed by
L‐arginine (1 mmol/L),
L‐arginine alone had no effect on GABA‐ and EFS‐induced relaxation in diabetic rats.

4. These results suggest that STZ‐induced diabetes impairs non‐adrenergic, non‐cholinergic relaxation induced by EFS and GABA. Impairment of nitrergic innervation of the rat duodenum may contribute to the abnormalities of intestinal motility abnormalities associated with diabetes.
VASCULAR COMPLICATIONS OF DIABETES MELLITUS
Authors: Yuan Shenyuan , Liu Yuantao , Zhu Liangxiang
Published: March 2003

1. Macro‐ and microvascular diseases are the main chronic complications of diabetes mellitus (DM).

2. It has been shown that DM patients have more severe nailfold microcirculatory disturbances than patients with liver cirrhosis or systemic lupus erythematosus (SLE).

3. It has been shown that the glomerular basement membrane of diabetic rats is significantly thickened compared with that of normal rats (295.5±45.1 vs 184.8±33.2 nm).

4. Gastric mucosal blood flow (GMBF) in 41 patients with non‐insulin‐dependent diabetes mellitus (NIDDM) was determined with a laser Doppler flowmeter. The results showed that average GMBF values at 14 sites in the gastric mucosa were significantly lower in NIDDM patients than in control subjects.

5. The percentage of painless acute myocardial infarction (AMI) among 50 patients with DM was 22.0% and the mortality of AMI was 22.0% (11 cases). Both these values were higher than the corresponding values in patients without DM (9.9 and 11.4%, respectively; P < 0.05).

6. Cerebrovascular disease is more prevalent in diabetic patients than in non‐diabetics and the mortality of stroke in DM patients is two‐fold higher than that of non‐diabetic patients.

7. Diabetes can result in widespread macrovascular atherosclerosis and microcirculatory disorders of multiple organs.
Salt‐ And Angiotensin Ii‐Dependent Variations In Amiloride‐Sensitive Rectal Potential Difference In Mice
Authors: Wang Qing , Horisberger Jean‐Daniel , Maillard Marc , Brunner Hans R , Rossier Bernard C , Burnier Michel
Published: March 2003

1. In the rectum and distal nephron, sodium reabsorption is mediated by the amiloride‐sensitive epithelial sodium channel (ENaC). The ENaC‐mediated sodium transport is electrogenic and creates an amiloride‐sensitive transepithelial potential difference (PD).

2. We have evaluated the salt‐ and angiotensin (Ang)II‐dependent variations in amiloride‐sensitive rectal PD in mice and assessed their relationship with renal sodium handling.

3. Rectal PD was measured in vivo in mice maintained on a medium‐, low‐ or high‐sodium diet. On a medium‐salt diet, the mean (±SEM) amiloride‐sensitive PD was larger in the afternoon than in the morning (–26.1±0.9 and –11.2±0.7 mV, respectively; P = 0.001), indicating a circadian cyclicity. Rectal PD increased on a low‐sodium diet and decreased on a high‐sodium diet.

4. Amiloride‐sensitive rectal PD correlated significantly with the urinary Na+/K+ ratio (P < 0.001) and with sodium reabsorption in the distal nephron as measured by the lithium clearance technique (P < 0.001).

5. In mice treated with an AngII AT1 receptor antagonist, amiloride‐sensitive rectal PD was increased in the afternoon compared with controls (–32.8±2.0 vs–24.4±0.9, respectively; P < 0.001).

6. At high doses, AngII decreased the amiloride‐sensitive rectal PD and this effect was blunted by an AT1 receptor antagonist.

7. These results show the presence of a salt‐dependent daily cyclicity of sodium transport in the mouse rectum that follows circadian changes in sodium handling in the distal nephron. Angiotensin II appears to modulate this diurnal pattern of rectal amiloride‐sensitive sodium transport.
Ginkgo Biloba Extract Attenuates The Development Of Hypertension In Deoxycorticosterone Acetate‐Salt Hypertensive Rats
Authors: Umegaki Keizo , Shinozuka Kazumasa , Watarai Ken , Takenaka Hiroyuki , Yoshimura Mika , Daohua Pang , Esashi Takatoshi
Published: March 2003

1. We examined the effects of Ginkgo biloba extract (GBE) on the development of hypertension, platelet activation and renal dysfunction in deoxycorticosterone acetate (DOCA)‐ salt hypertensive rats. Both DOCA‐salt hypertensive rats and normotensive rats were fed a 2% GBE diet for 20 days. Blood pressure (BP) was measured by two methods, namely by the tail‐cuff and telemetry methods.

2. Development of hypertension was attenuated in rats fed a 2% GBE diet. In addition, an increase in heart weight, an indicator of sustained high BP, was inhibited significantly by feeding of the GBE diet.

3. Decreases in 5‐hydroxytryptamine content in platelets, a marker of platelet activation in vivo associated with hypertension, were also prevented by feeding of the GBE diet. Ginkgo biloba extract itself did not inhibit ADP‐ and collagen‐induced platelet aggregation examined in vitro. Feeding of the GBE diet tended to inhibit increases in plasma urea nitrogen due to hypertension.

4. The telemetry study demonstrated that BP and heart rate (HR) showed a clear circadian rhythm and the anti‐ hypertensive effect of GBE was prominent in the daytime, a resting period for rats. This anti‐hypertensive effect of GBE was not detected in normotensive rats. In contrast, the inhibitory effect of GBE on HR was independent of time and was observed in both normotensive and hypertensive rats.

5. These results indicate that GBE has an anti‐hypertensive and bradycardiac action, which are time dependent and independent, respectively. Thus, it appears that the chronopharmacological action of GBE may be ascribed not to pharmacokinetic factors, but rather to a circadian susceptibility rhythm to GBE in DOCA‐salt hypertensive rats.
Isoproterenol‐Induced Hypertrophy May Result In Distinct Left Ventricular Changes
Authors: Murad Neif , Tucci Paulo Jf
Published: March 2003

1. The aim of the present study was to analyse the possible lack of uniformity in isoproterenol (ISO)‐induced myocardial hypertrophy.

2. Data obtained for isovolumic hearts isolated from 20 rats treated with ISO (0.3 mg/kg over 8 days) were divided into two groups (H1, n = 10; H2, n = 10) according to the volume (mean±SD) needed to change left ventricle diastolic pressure from 0 to 40 mmHg (H1, 184±30 μL; H2, 108±14 μL). Eight control rats (C; 165±37 μL) were used for comparison.

3. In addition to ventricular distensibility differences, the groups differed in terms of myocardial mass (mean±SEM: H1, 181±3 mg > H2, 166±3 mg > C, 136±3 mg; P < 0.001), of relaxation constant (H2, 43±4 msec > H1, 28±2 msec; P = 0.0012) and of maximum developed circumferential stress (C, 145±9 kdyn/cm
2 = H1, 137±6 kdyn/cm
2 > H2, 110±4 kdyn/cm
2; P = 0.002).

4. Our results show that ISO‐induced myocardial hypertrophy is not homogeneous. Data obtained for H2, taken as a whole and compared with H1 (smaller myocardial mass and impairment of relaxation, elastic stiffness and force generation), suggest that, in some animals, myocardial necrosis and reparative fibrosis may prevail over the stimulus for myocyte growth. The lack of uniformity of ISO‐induced myocardial hypertrophy has not been previously reported and may have contributed to the divergence observed in the literature regarding the functional characteristics of the present model.
Acute And Chronic Sympathoinhibition On Carotid Artery Diameter Of Spontaneously Hypertensive Rats: Effects Of Clonidine And Flesinoxan
Authors: Dabiré H , Chamiot‐Clerc P , Chaouche‐Teyara K , Fournier B , Safar Me
Published: March 2003

1. Hypertensive conduit arteries are thicker and stiffer than those of normotensive controls. Whether they are specifically sensitive to central sympathoinhibition has never been investigated.

2. The effects of acute (24 h infusion) and chronic (4 week infusion) treatments with clonidine (0.01 and 0.1 mg/kg per day) and flesinoxan (1 and 3 mg/kg per day) on carotid artery diameter were investigated in spontaneously hypertensive rats. At the end of treatment, blood pressure (BP) was recorded in the rats while they were conscious. Rats were then anaesthetized for carotid artery diameter measurements using an ultrasonic echo‐tracking device.

3. In conscious rats, clonidine significantly decreased BP and heart rate (HR) following acute but not chronic treatment. In contrast, flesinoxan significantly decreased BP following both the acute and chronic treatment. In anaesthetized animals, the two agents have opposite effects on isobaric carotid artery diameter, with a decrease under clonidine and an increase under flesinoxan. After 4 weeks infusion, the reactivity of aortic rings was studied in organ chambers. Flesinoxan, but not clonidine, caused the relaxation of potassium chloride precontracted aortic segments.

4. The results indicate that although clonidine and flesinoxan are centrally acting antihypertensive agents, the drug‐induced changes in isobaric carotid diameter may be influenced by local factors independent of the central action of the two drugs.
Effects Of Trilinolein On Superoxide Dismutase Activity And Mrna Levels In Aortic Smooth Muscle Cells
Authors: Chan Paul , Chang Jun‐Jen , Chen Fu‐Chean , Wu Ming‐Shun , Tomlinson Brian , Cheng Juei‐Tang
Published: March 2003

1. Atherosclerotic cardiovascular disease is still the leading cause of death in Western countries. Oxygen free radicals are considered to be intimately involved in the development of atherosclerosis. Anti‐oxidants may help to protect mammalian cells from the damage induced by these reactive oxygen species. Many reports have indicated that anti‐oxidants used in the treatment or prevention of disease could modify the levels of superoxide dismutase (SOD). However, the effects of long‐term anti‐oxidant treatment on the levels of SOD in smooth muscle cells (SMC) is still unclear. In the present study, the effects of the lipophilic anti‐oxidant trilinolein on the activity and gene expression of SOD in SMC were evaluated.

2. After 2 days incubation with 0.1 μmol/L trilinolein, the activity and mRNA levels of SOD were increased in rat aortic SMC (A7r5), but there was no significant change in these parameters with a higher concentration of 1 μmol/L trilinolein.

3. In contrast, after 7 days incubation with trilinolein, both the activity and mRNA levels of SOD were lowered in a dose‐dependent manner.

4. These data emphasize the importance of choosing an optimal dosage for supplementation with anti‐oxidants in humans for the scavenging of oxygen free radicals.
Effect Of A Series Of Novel Sulphonylthioureas On Glucose Tolerance In The Obese fa/fa Zucker Rat
Authors: Farrar Nicole S , Chambers Noel J , Carlsson Anthony R , Denyer Gareth , Johnston Graham Ar
Published: March 2003

1. The recent development of a series of novel KATP channel modulators, namely sulphonylthioureas and sulphonylureas, is thought to make improvements in potency and tissue selectivity compared with current sulphonylureas, such as glibenclamide, which shares a similar structure to the novel compounds.

2. These novel compounds were first examined for their effect on hyperglycaemia and glucose tolerance during an oral glucose tolerance test following 5 days administration in the lean fa/– and obese fa/fa Zucker rat (a model of insulin resistance). Comparisons with present antidiabetic agents, metformin and glibenclamide were performed.

3. Several compounds showed improvements in glucose tolerance compared with control and the primary structural prerequisites for the maintenance of this activity were investigated. Of most interest was compound 3–15 ((N‐[(4‐methylphenylsulphonyl]‐N′‐(2‐ethoxypyrid‐4‐yl)thiourea; 0.1 mg/kg per day), which significantly improved glucose tolerance following 5 days administration in the fa/fa Zucker rat. This paralleled the improvement seen in metformin (300 mg/kg per day)‐treated fa/fa rats, but compound 3–15 was up to 3000‐fold more potent than metformin.

4. Obese fa/fa Zucker rats were then treated with compound 3–15 for 28 days to determine whether glycaemic control could be maintained over the longer term.

5. Compound 3–15 showed a significant improvement in glucose clearance and reduction in insulin concentration following 28 days treatment during an intravenous glucose tolerance test compared with untreated rats, without any change in the rate of weight gain.

6. The novel sulphonylthiourea 3–15 appears to improve glucose clearance during acute and chronic treatment in the fa/fa Zucker rat with no effect on the rate of weight gain. It is thought that compound 3–15 may be eliciting its actions by improving insulin sensitivity, but its effects on insulin secretion are still to be elucidated.
Effects Of L‐Arginine And Furosemide On Blood Pressure And Renal Function In Volume‐Expanded Rats
Authors: Costa Ma , Marchetti M , Balaszczuk Am , Arranz Ct
Published: March 2003

1. The aim of the present study was to investigate the effects of L‐arginine (L‐Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume‐expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L‐Arg in this model.

2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L‐Arg, 1 mg/kg NG‐nitro‐L‐arginine methyl ester (L‐NAME), FUR + L‐NAME or FUR + L‐Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined.

3. Extracellular fluid volume expansion induced no changes in MAP in control and volume‐expanded rats (92±6 vs 100±8 mmHg, respectively). The hypotension induced by FUR in control and volume‐expanded rats (69±7 and 76±5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L‐Arg (54±3 and 64±3 mmHg, respectively).

4. Injection of L‐NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups.

5. Furosemide‐induced water and electrolyte excretion was blunted by the administration of L‐NAME.

6. The combination of L‐Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33±1.68 vs 12.91± 0.41 μL/min per 100 g, respectively; volume‐expanded rats: 248.5±25.4 vs 112,6±8.3 μL/min per 100 g, respectively; P < 0.01).

7. The administration of the combination of L‐Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230±0.018 vs 0.45±0.03, respectively, P < 0.001; volume‐expanded rats: 0.091±0.010 vs 0.22±0.03, respectively, P < 0.01).

8. The potassium/water excretion rate induced by FUR alone and in the presence of L‐Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35±0.05 vs 0.20±0.05 μEq/min per 100 g, respectively; volume‐expanded rats: 0.045±0.008 vs 0.014±0.003 μEq/min per 100 g, respectively; P < 0.01).

9. The decrease in the electrolyte/water excretion ratio observed with FUR + L‐Arg in volume‐expanded rats was greater than in control animals.

10. The results of the present study show that the administration of FUR with L‐Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.
Insulin‐Like Effect Of (–)Epicatechin On Erythrocyte Membrane Acetylcholinesterase Activity In Type 2 Diabetes Mellitus
Authors: Rizvi Syed Ibrahim , Zaid Mohammad Abu
Published: March 2003

1. Changes in the activity of acetylcholinesterase (AChE) have been reported in diabetes mellitus that have been linked to certain brain defects. The erythrocyte membrane AChE is reported to be similar to AChE present in the brain.

2. Epicatechin, a member of a group of polyphenolic compounds collectively known as ‘catechins’ that are present in tea and belong to the flavonoid family, has been reported to possess insulin‐like activity.

3. In the present study, the in vitro effect of (–)epicatechin and/or insulin was tested on erythrocyte membrane AChE in normal and type 2 diabetic patients. The aim of the study was to test the efficacy of (–)epicatechin to mimic insulin in its effect on erythrocyte membrane AChE.

4. Acetylcholinesterase activity was significantly lower in type 2 diabetic patients than in normal controls and in vitro insulin treatment restored this activity to normal levels. Epicatechin (1 mmol/L) also caused an elevation in AChE activity in diabetic erythrocytes, an effect that was similar to the effect of insulin.

5. Epicatechin has a pronounced insulin‐like effect on erythrocyte membrane‐bound AChE in type 2 diabetic patients; however, the mechanism of action of epicatechin remains speculative.
Familial Varieties Of Primary Aldosteronism
Authors: Stowasser Michael , Gunasekera Thanuja G , Gordon Richard D
Published: March 2003

1. Improved approaches to screening and diagnosis have revealed primary aldosteronism (PAL) to be much more common than previously thought, with most patients normokalaemic. The spectrum of this disorder has been further broadened by the study of familial varieties.

2. Familial hyperaldosteronism type I (FH‐I) is a glucocorticoid‐remediable form of PAL caused by the inheritance of an adrenocorticotrophic hormone (ACTH)‐ regulated, hybrid CYP11B1/CYP11B2 gene. Diagnosis has been greatly facilitated by the advent of genetic testing. The severity of hypertension varies widely in FH‐I, even among members of the same family, and has demonstrated relationships with gender, degree of biochemical disturbance and hybrid gene crossover point position. Hormone “day curve” studies show that the hybrid gene dominates over wild‐type CYP11B2 in terms of aldosterone regulation. This may be due, in part, to a defect in wild‐type CYP11B2‐induced aldosterone production. Control of hypertension in FH‐I requires only partial suppression of ACTH and much smaller glucocorticoid doses than previously recommended.

3. Familial hyperaldosteronism type II (FH‐II) is not glucocorticoid remediable and is not associated with the hybrid gene mutation. Familial hyperaldosteronism type II is clinically, biochemically and morphologically indistinguishable from apparently non‐familial PAL. Linkage studies in one informative family did not show segregation of FH‐II with the CYP11B2, AT1 or MEN1 genes, but a genome‐wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH‐I, elucidation of causative mutations is likely to facilitate earlier detection of PAL.
Adaptations Of Skeletal Muscle To Prolonged, Intense Endurance Training
Authors: Hawley John A
Published: March 2003

1. Endurance exercise induces a variety of metabolic and morphological responses/adaptations in skeletal muscle that function to minimize cellular disturbances during subsequent training sessions.

2. Chronic adaptations in skeletal muscle are likely to be the result of the cumulative effect of repeated bouts of exercise, with the initial signalling responses leading to such adaptations occurring after each training session.

3. Recently, activation of the mitogen‐activated protein kinase signalling cascade has been proposed as a possible mechanism involved in the regulation of many of the exercise‐induced adaptations in skeletal muscle.

4. The protein targets of AMP‐activated protein kinase also appear to be involved in both the regulation of acute metabolic responses and chronic adaptations to exercise.

5. Endurance training is associated with an increase in the activities of key enzymes of the mitochondrial electron transport chain and a concomitant increase in mitochondrial protein concentration. These morphological changes, along with increased capillary supply, result in a shift in trained muscle to a greater reliance on fat as a fuel with a concomitant reduction in glycolytic flux and tighter control of acid–base status. Taken collectively, these adaptations result in an enhanced performance capacity.
Capsazepine Partially Inhibits Neurally Mediated Gastric Mucus Secretion Following Activation Of Protease‐Activated Receptor 2
Authors: Kawabata Atsufumi , Kinoshita Mitsuhiro , Kuroda Ryotaro , Kakehi Kazuaki
Published: March 2003

1. Protease‐activated receptor 2 (PAR2), present in capsaicin‐sensitive sensory neurons, induces gastric mucus secretion and mucosal cytoprotection.

2. We studied the possible cross‐talk between PAR2 and vanilloid receptor 1 (VR1). The VR1 antagonist capsazepine partially inhibited the PAR2‐mediated increase in gastric mucus secretion.

3. Thus, activation of VR1 is responsible, at least in part, for the neurally mediated mucosal cytoprotection following activation of PAR2.
Effect Of α‐Lipoic Acid On Lipid Peroxidation And Anti‐Oxidant Enzyme Activities In Diabetic Rats
Authors: Dinçer Yıldız , Telci Ayşegül , Kayalı Refik , Yılmaz İlker A , Çakatay Ufuk , Akçay Tülay
Published: March 2003

1. Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. Recently, α‐lipoic acid (ALA) has gained considerable interest as an anti‐oxidant. Various studies have indicated the anti‐ oxidant effects of ALA and its reduced form dihydrolipoic acid. Therefore, it appears that these compounds have important therapeutic potential in conditions where oxidative stress is involved. The aim of the present study was to investigate the effect of ALA supplementation on lipid peroxidation and anti‐oxidant enzyme activities in various tissues in diabetic rats.

2. Male Wistar rats were divided into three groups. Diabetes was induced by streptozotocin (STZ) injection in the two groups of rats to be supplemented and not to be supplemented with ALA. Another group of rats, which received saline injection, formed the control group. After 5 weeks of diabetes, rats were killed. In order to assess the redox status of various organs in the diabetic and control rats, thiobarbituric acid‐reactive substances (TBARS) and glutathione (GSH) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (G‐Px) and glutathione reductase (G‐Red) activities were determined in the liver, pancreas and kidney.

3. In both diabetic groups, TBARS levels and SOD activity were increased in the liver and pancreas, G‐Px and G‐Red activities were increased in the kidney and GSH levels were decreased in all organs compared with controls. In the ALA‐ supplemented group, TBARS levels were decreased, GSH levels were increased in the liver and pancreas, SOD activity was decreased in the liver, G‐Px activity remained unchanged in all tissues and G‐Red activity was increased in the pancreas compared with the diabetic group that did not receive ALA supplementation.

4. In conclusion, ALA supplementation has disparate effects on the redox status of different organs. These data are not sufficient for confirmation the beneficial effects of ALA supplementation on the redox status of various organs in diabetic rats.
Myocardial Energetics In Cardiac Hypertrophy
Authors: Zhang Jianyi
Published: March 2003

1. This review is presented with the intent of illustrating the representative studies of functional and myocardial energetic consequences of hearts with postinfarction left ventricular (LV) remodelling or with concentric hypertrophy and diastolic LV dysfunction in porcine models.

2. Both eccentric and concentric cardiac hypertrophy are associated with the abnormal myocardial energetics that are most severe in hearts with congestive heart failure (CHF). Presently, these abnormalities cannot be satisfactorily explained to be the cause(s) of the dysfunction of failing hearts or cause the progress from compensated cardiac hypertrophy to CHF.

3. Mechanisms governing abnormal myocardial high‐energy phosphate (HEP) metabolism in hearts with cardiac hypertrophy and CHF are unclear. Myocardial energy metabolism studies use both kinetic and thermodynamic models. The thermodynamic studies examine the myocardial steady state levels of high‐ and low‐energy phosphate, which indicate myocardial energy state or phosphorylation potential that is defined by the ratio of [ATP]/([ADP][Pi]). The kinetics studies examine the reaction velocity that is regulated by: (i) quantity and activity of the key enzymes; (ii) the concentrations of all the substrates and products; and (iii) the Michaelis–Menten constants of each substrate of the reaction.

4. Significant alterations in myocardial concentrations of phosphocreatine (PCr), ATP and ADP, myocardial oxidative phosphorylation (OXPHOS) protein expression and substrate preference are found in hearts with postinfarction LV remodelling and CHF. However, to define a causal relationship is a different matter.

5. Future studies of animal models of LV hypertrophy or heart failure using gene manipulation may provide additional insights to answer the persisting question of whether limitations of ATP synthetic or transport capacities contribute to the pathogenesis of LV remodelling or failure.
Role Of Trophic Factors In The Development, Survival And Repair Of Primary Auditory Neurons
Authors: Marzella Phillip L , Gillespie Lisa N
Published: March 2003

1. Neurotrophic factors have been identified as crucial for the development of the auditory system and have also been proven to be important for continued survival and maintenance of auditory neural connections.

2. In addition, both in vitro and in vivo studies have demonstrated that these trophic molecules can prevent the secondary wave of auditory neuron degeneration normally seen following the loss of hair cells.

3. Furthermore, neurotrophic factors have been reported to enhance neuronal excitation and to improve the efficacy of synaptic transmission.

4. As such, these molecules are strong candidates to be used as therapeutic agents in conjunction with the cochlear implant, or even to repair and/or regenerate damaged or lost auditory nerve and sensory cells.