To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream. Twenty-four male Wistar rats (300-350g) were obtained from the ANILAB , barrier facility and maintained on light/dark cycles of 12 hours, and fed a standard rodent chow diet. They were deprived of food, but not water, for 12h prior to the surgical procedure. Diversion of fecal stream was performed in all animals similar as previous described Twenty-four animals were divided into two experimental groups with 12 animals each according the euthanasia had done after 2 or 4 weeks of treatment. These two experimental groups were divided into four subgroups with six animals each according to the intervention solution employed and time of intervention. In the first and second subgroups, six animals received daily rectal enemas containing 20 ml of saline (control subgroup) at 37ºC, and six received daily rectal enemas containing 20 ml of MEZ  at concentration of 100 mg/kg for 2 weeks. In the 12 remaining animals of the second group, six rats received daily rectal enemas with saline and six with MEZ at same concentration for 4 weeks. In order to standardize the speed and time of application, the enemas were administered in all animals with an infusion pump whose speed was standardized at 5/ml/min.  Upon completion of the pre-determined irrigation period, the animals were anesthetized with the same technique used to diversion of the fecal stream, and the midline incision was opened again. In both groups, specimens were taken from the intra-abdominal part of the excluded colon . The removed specimens of the colon without fecal stream, measuring approximately 6.0 cm each, was longitudinally opened through the anti-mesenteric border fixed in a piece of cork and referred to histological and histochemical analysis. Fragments prepared for histological analysis were immersed in 10% neutral formalin buffer  for 24 h, dehydrated by exposure to increasing ethanol concentrations and embedded in paraffin. Thereafter, sections of tissue were cut at 5 µm on a rotary microtome , mounted on a glass slide, cleared, hydrated and stained with hematoxylin-eosin (HE) for evaluation of the presence of colitis. Slide analysis was performed with optical microscope  with final magnification of x200. To establish the diagnosis of colitis, as well as the degree of inflammation, the histological slides were analyzed by two blinded observers. The diagnosis of colitis was made based on presence of five independent histological parameters: reduction of the crypt length, number of goblet cells, crypt abscess, intensity of neutrophil infiltration of the mucosa, and epithelial loss. These variables were stratified as crosses, according to the degree of each, as follows: 0: absent or no alterations; (+): when intensity was mild; (++): moderate and, (+++): intense. For all variables analyzed, the final value considered for each animal was the mean value after quantification of three distinct histological fields. The inflammatory score for each animal was obtained from the sum of the five variables analyzed. The tissue expression of the neutral and acid mucins was determined by histochemical technique of Periodic Acid Schiff (PAS) and Alcian-blue (AB), respectively, as previous report The neutral and acid mucin content, as well the tissue content of sulfomucins and sialomucins, was quantified by means of computer-assisted image processing and was always performed in a focal field in which there were at least three complete and contiguous colonic glands, at a magnification of x200. A pathologist with experience of IBD, who was unaware of the origin of the material and the objectives of the study, evaluated the content of tissue expression of all types and subtypes of mucins. The images selected were captured on a video camera that had been coupled to an optical microscope. These images were processed and analyzed using the NIS-Elements 3.1 software . By means of colored histograms in the red, green and blue (RGB) system, the software determined the color intensity and the number of pixels in each selected field, and the final data were transformed into percentage expression of mucins per field analyzed (%/field). The final value measured for each section was the mean of the values found from evaluating three different fields. The tissue content of sulfomucins and sialomucins was quantified in the same colonic glands.•) when this level was less than 5% or two tickets (••) when this level was less than 1%. The results obtained for the tissue contents of all types and subtypes of mucins were always described by the mean value with respective standard error. A significance level of 5% (p<0.05) was adopted for all tests. The Mann-Whitney test was used to compare the degree of inflammation, the tissue content of the all types of mucins of animals from the control  and experimental (MEZ) groups and to compare colon segments submitted to intervention with saline or MEZ for two or four weeks. BioStat software (version 5.1) was used for the statistical analysis. Significant values when were compared colon segments without fecal stream irrigate with saline or MEZ, were marked with asterisk (*) when this level was less than 5% or two asterisks when this level was less than 1% . At the same way, the significant values found when the animals submitted to the intervention with saline or MEZ by two or four weeks were marked with one ticket ( In  In  The mean values, with the respective standard error, for the inflammatory score, tissue content of neutral, acid mucins, sulfomucins and sialomucins, in colon segments without fecal stream, of the animals submitted to intervention with saline or MEZ, for two or four weeks are show in ,,,, The colonic mucosal barrier is made up of epithelial and immune cells which together form a barrier to harmful agents. The colonic epithelium is covered by a thick layer of mucus that serves as a first line of the colonic epithelium defense system,MUC2 gene expression, stimulated mucin synthesis thereby increasing the thickness of the mucus layer that covers the colonic epithelium,,, There are several evidences suggesting that SCFAs reinforces the colonic defense barrier mainly by stimulating the synthesis of mucins,,,,,,,, Deficiency of SCFAs colonic mucosa cells could potentially increase production of ROS, resulting in onset of mucosal inflammation ,,-,-,,,,-- Experimental studies evaluated the effects of oxidative stress and substances with antioxidant properties on the tissue content of neutral an acidic mucins in the colonic mucosa with and without fecal streamex vivo challenge with H2O2 The results of the present study seems to confirm the antioxidant action of MEZ in protect the colonic mucosa devoid of the fecal stream. Enemas with MEZ were able to reduce the mucosa inflammation and maintain the tissue content of neutral and acids mucins despite the lack of supply of SCFAs. Regardless of the time of intervention adopted, the tissue content of neutral and acidic mucins was always higher in animals treated with MEZ when compared with those treated with saline. There was an increase in the tissue content of acid mucins with the intervention time. Animals treated with MEZ also had an improvement in the inflammatory score when compared to those treated with saline. It is possible that these findings are related to the reduction of levels of oxidative damage. In a previous study, utilizing the same group of animals, we showed that the application of enemas with MEZ was able to reduce the levels of oxidative damage to the DNA of the isolate cells obtained from colonic segments devoid of fecal transit, even after et al.,,- Keli , The results of this study seems to confirm the action of MEZ in maintain the tissue content of sulfomucins and sialomucins in colonic mucosa devoid of the fecal stream. Regardless of the time of intervention adopted, the tissue content of sulfomucins and sialomucins mucins was always higher in animals treated with MEZ when compared with those treated with saline. There was an increase in the tissue content only of sulfomucins with the intervention time. Although the sialomucins are the subtype of acid mucin that presents the greatest reduction of its contents in colonic mucosa excluded from fecal stream, the tissue content of sialomucins was always higher in animals treated with MEZ when compared with those treated with saline. These same results were found by other authors who used enemas with antioxidant substances in the mucosa devoid of fecal stream,,,,,, These results reinforce the possibility that oxidative stress caused by overproduction of ROS by epithelial cells devoid of fecal stream may be related to the reduction of the mucins contents. The data confirm the benefits of MEZ in the treatment of DC, as demonstrated by its therapeutic effects at increasing the production of the all types and subtypes of mucins studied. Previous experimental studies showed that the use of enemas containing MEZ could reduce levels of oxidative damage in cells of chronically inflamed colonic mucosa, and may be this one of the most important mechanism related to reduction of the mucins content Daily enemas with MEZ can improve the inflammatory process and increase the tissue content of mucins in colonic mucosa devoid of the fecal stream in an experimental model of diversion colitis.


Until recently, trophoblast invasion during human placentation was characterized by and restricted to invasion into uterine connective tissues and the uterine spiral arteries. The latter was explained to connect the arteries to the intervillous space of the placenta and to guarantee the blood supply of the mother to the placenta. Today, this picture has dramatically changed. Invasion of endoglandular trophoblast into uterine glands, already starting at the time of implantation, enables histiotrophic nutrition of the embryo prior to perfusion of the placenta with maternal blood. This is followed by invasion of endovenous trophoblasts into uterine veins to guarantee the drainage of fluids from the placenta back into the maternal circulation throughout pregnancy. In addition, invasion of endolymphatic trophoblasts into the lymph vessels of the uterus has been described. Only then, invasion of endoarterial trophoblasts into spiral arteries takes place, enabling hemotrophic nutrition of the fetus starting with the second trimester of pregnancy. This new knowledge paves the way to identify changes that may occur in pathological pregnancies, from tubal pregnancies to recurrent spontaneous abortions. The last years have seen a massive evolution of omics and sequencing technologies that finally allow single-cell sequencing and profiling. Single-nucleus RNA sequencing per droplet (DroNc-Seq)  has been proposed in 2002 . The disadvantage of using a cytokeratin antibody is that it also identifies other epithelial cells such as the epithelium of uterine glands. Hence, a missing differentiation between invading trophoblasts and glandular epithelial cells may have misled scientists  , but also differs in a variety of features (B–E):(A)Interstitial trophoblasts invade through the uterine interstitium, finally reaching the outer aspects of the arterial wall. Endoarterial trophoblasts percolate through the vessel wall, restructure the arterial media, displace the arterial endothelium and finally migrate into the lumen of the arteries During the first trimester, the endoarterial trophoblasts do not only reach and line the inner wall of the arteries, but also fill the lumen by building plugs of endoarterial trophoblasts Different from veins and glands, arterial invasion by endoarterial trophoblasts leads to transformation of the vessel walls resulting in large conduits that are no longer under vasomotor control of the mother.(D)Different from veins and glands, flow of maternal blood through arteries into the intervillous space of the placenta only starts at the beginning of the second trimester Different from veins and glands, endoarterial trophoblasts also invade into the deeper regions of the arterial walls, finally reaching the portions of the arteries within the inner third of the myometrium. Veins and glands only need to be connected to the intervillous space of the placenta, while arteries need to be connected plus transformed and widened to enable a slow inflow of maternal blood into the intervillous space  from the subclavian veins in the junction with the jugular veins . As described above, extravillous trophoblasts are known to invade uterine spiral arteries starting at around mid-first trimester  and lymphatics (endolymphatic trophoblast) and may well be washed into the maternal blood stream. Thus, they could be responsible for the presence of fetal cells and DNA in maternal blood from week 6 onward  is defined by the occurrence of three or more consecutive miscarriages before 20 weeks of gestation. In cases of idiopathic RSA, the role of arterial trophoblast invasion has historical roots but still remains controversial  than healthy controls (Windsperger et al. Implantation sites within the uterus and the fallopian tube are similar in composition and cell density of the tissues comprising the surface epithelium and the lamina propria of the tubal or uterine wall containing connective tissue, glandular and surface epithelium, trophoblast cells and lymphocytes (Kemp et al. Extravillous trophoblasts invade into much more luminal structures in the maternal decidua than was known until today. It seems as if extravillous trophoblasts invade into each luminal structure that is present along their invasive pathway. Hence, it seems as if there is no restriction of trophoblast invasion in terms of specificity of invaded structures. The elucidation of alterations of trophoblast invasion in pregnancy pathologies has only just begun. The following years will tell how many of the alterations have been missed so far and may explain pathologies such as recurrent spontaneous abortions and fetal growth restriction.


The Kentucky (KY) Rural & Underserved Geriatric Interprofessional Education Program (KRUGIEP) participated in a unique innovative approach to the implementation of the Medicare Annual Wellness visit in collaboration with the Dartmouth GWEP. The model focused on the integration of students into the process of conducting the Health Risk Assessment through community based home visits. This talk will focus on this unique program and the participation in a multi-GWEP learning collaborative.


The facial artery is the main artery of the face and variations in its origin and its branching pattern have been documented. We report herein multiple facial artery branch variations in the face. A large posterior (premasseteric) branch originated from the left facial artery and coursed upwards behind the main trunk of the facial artery. This artery presented with a straight course and was closely related to the anterior border of the masseter. The branch then terminated by supplying the adjacent connective tissue below the parotid duct. It was also observed that the facial artery was very thick and tortuous and terminated as the superior labial artery. Knowledge of this variation is of great clinical significance in facial operations, especially for maxillofacial surgeons and plastic surgeons, because it forms the anatomical basis for the facial artery musculo-mucosal flap. The face is supplied by branches of the facial artery and the superficial temporal arteries. The facial artery originates in the neck, arising from the external carotid artery, and terminates at the medial angle of the eye. This artery’s tortuosity allows it to stretch during various movements of the jaw. The branches of the facial artery in the face are the superior labial artery, inferior labial artery, and the lateral nasal artery, which supply the muscles and skin of the face. It also gives off a few small unnamed branches posteriorly.The facial artery presents variations with regards to its origin, termination, course, and branching pattern. We report herein a variant termination of the facial artery and the occurrence of a large posterior branch of the facial artery known as the premasseteric artery. This is a minor inconsistent branch,During dissections for undergraduate medical students, we found unusual variations in the branching pattern and termination of the left facial artery in the face. These variations were observed in a male cadaver aged about 65-70 years. The left facial artery presented a large posterior branch (premasseteric branch) which coursed upwards parallel to the facial artery . After iVariations related to the facial artery or its branches have two aspects of interest: In operations of the face and lip, during reconstructive and reparative procedures, and in radiologic anatomy, in the field of malignancy for the treatment of some facial tumors by embolization. There are reports in the literature of variations in the origin, termination, and branches of the facial artery. The premasseteric branch is an uncommon branch that was first described by Adachi in 1928.Bayram et al. has studied variations of the facial artery in fetuses.The face is richly vascularized and so construction of several facial flaps is possible. Reconstruction of lip defects using procedures like the Abbe flap and other lip flap procedures involves surgical manipulation of one of the major facial artery branches, mainly the superior labial artery.Maxillofacial and plastic surgeons must have detailed knowledge of such variations before deciding on any grafts or surgical interventions on the face. Knowledge regarding such variations is also imperative for general surgical practitioners and specialists, for the effective management of any injuries, or correction of congenital anomalies like cleft lip and palate. Such anomalous variations therefore warrant use of a noninvasive in vivo technique for evaluation of the facial artery anatomy in order to facilitate preoperative planning in complex facial reconstructions.


This review describes the preparation of the hSV as a bypass conduit in CABG and its performance compared with the ITA as well as how and why its patency might be improved by harvesting with minimal trauma in a way that preserves an intact vasa vasorum.The saphenous vein (SV) is the most commonly used conduit for revascularization in patients undergoing coronary artery bypass surgery (CABG). The patency rate of this vessel is inferior to the internal thoracic artery (ITA). In the majority of CABG procedures the ITA is removed with its outer pedicle intact whereas the (human) SV (hSV) is harvested with pedicle removed. The vasa vasorum, a microvessel network providing the adventitia and media with oxygen and nutrients, is more pronounced and penetrates deeper towards the lumen in veins than in arteries. When prepared in conventional CABG the vascular trauma caused when removing the hSV pedicle damages the vasa vasorum, a situation affecting transmural flow potentially impacting on graft performance. In patients, where the hSV is harvested with pedicle intact, the vasa vasorum is preserved and transmural blood flow restored at graft insertion and completion of CABG. By maintaining blood supply to the hSV wall, apart from oxygen and nutrients, the vasa vasorum may also transport factors potentially beneficial to graft performance. Studies, using either corrosion casts or India ink, have shown the course of vasa vasorum in animal SV as well as in hSV. In addition, there is some evidence that vasa vasorum of hSV terminate in the vessel lumen based on  In a recent issue of Nature Reviews in Cardiology de Vries and colleagues discuss the use of the saphenous vein (SV) as a conduit for surgical revascularization in patients undergoing coronary artery bypass graft surgery (CABG)  endothelial integrity is maintained even in the absence of intraluminal blood flow . However, it is important to stress that at present little is known regarding the luminal termination of vasa in hSV used for CABG. The most compelling evidence has been previously described in canine SV, where it is known that such terminations of vasa at the SV lumen can be opened by a complex structure – the agger, which is sensitive to changes in blood turbulence and conditions affecting flow through vasa microvessels  blood. The vasa vasorum of veins are classically described as being situated within the adventitia and the media Ham  with somThe study by Loop et al.  showed tThe advantages of the NTSVG technique is becoming recognised and the technique adopted by an increasing number of cardiac centres worldwide. Indeed, the recent review by deVries and colleagues  may be limited and may not reflect the true physiological events that occur in vivo hSV when used in CABG patients.Whereas the majority of studies relating to the effect of hypoxia in vessel pathology have been mostly on arteries, some have also included hSV material. The importance of maintaining blood and oxygen supply to all layers of the vessel wall has recently been supported by an elegant A porcine model of SV into artery interposition grafting has been described where the effect of external synthetic stents and sheaths on vein graft remodelling and thickening have been studied (Violaris et al. While a considerable amount of data has been published regarding the role of the vasa vasorum in pathological conditions in human arteries, in particular the epicardial coronary arteries, there is less information available on the SV. Reducing medial blood flow and oxygen supply by occluding the vasa vasorum in arteries causes neointima formation and atherosclerosis via the action of a vast number of hypoxia-induced factors. Since the role of the vasa vasorum in providing oxygen to the wall of the SV is more important than in arteries it seems reasonable to assume that anything reducing blood flow through this microvessel network will produce similar, or more serious, consequences. The considerable damage caused to the vasa vasorum when using CT harvesting described in earlier sections of this review will reduce medial blood flow stimulating a plethora of hypoxia-induced factors involved in vein graft failure Fig. . If the The vasa vasorum of the hSV plays a more important role in providing oxygen and nutrients to the vessel wall than in arterial bypass grafts, the ITA and RA. Consequently, this microvascular network is more prolific in the SV than the ITA or RA and extends deeper in the media with some evidence of terminations in the lumen. Furthermore, the connection of vasa vasorum to capillaries within the PVAT surrounding the hSV suggests that, apart from supplying blood, this microvascular network may potentially transport tissue- and/or cell-derived factors from the outermost to the innermost layers of this blood vessel or vice versa. The damage caused to the vasa vasorum of the hSV during conventional harvesting in CABG reduces transmural blood supply, a situation that promotes neointimal hyperplasia and atheroma formation, features associated with mid- and long-term graft patency. If the hSV is harvested with minimal vascular trauma, the vasa vasorum remains intact and arterial blood flow is restored at completion of graft insertion. In addition, an intact vasa vasorum may provide a system for the transport of factors and cell to cell communication across the hSV graft wall that are beneficial to improved graft performance.