Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation.

Here, by using in vitro and ex vivo approaches, we elucidate the impairment of the hydrogen sulfide (H2S) pathway in vascular complications associated with metabolic syndrome (MetS). In the in vitro model simulating hyperlipidemic/hyperglycemic conditions, we observe significant hallmarks of endothelial dysfunction, including eNOS/NO signaling impairment, ROS overproduction, and a reduction in CSE-derived H2S. Transitioning to an ex vivo model using db/db mice, a genetic MetS model, we identify a downregulation of CBS and CSE expression in aorta, coupled with a diminished L-cysteine-induced vasorelaxation. Molecular mechanisms of eNOS/NO signaling impairment, dissected using pharmacological and molecular approaches, indicate an altered eNOS/Cav-1 ratio, along with reduced Ach- and Iso-induced vasorelaxation and increased L-NIO-induced contraction. In vivo treatment with the H2S donor Erucin ameliorates vascular dysfunction observed in db/db mice without impacting eNOS, further highlighting a specific action on smooth muscle component rather than the endothelium. Analyzing the NO signaling pathway in db/db mice aortas, reduced cGMP levels were detected, implicating a defective sGC/cGMP signaling. In vivo Erucin administration restores cGMP content. This beneficial effect involves an increased sGC activity, due to enzyme persulfidation observed in sGC overexpressed cells, coupled with PDE5 inhibition. In conclusion, our study demonstrates a pivotal role of reduced cGMP levels in impaired vasorelaxation in a murine model of MetS involving an impairment of both H2S and NO signaling. Exogenous H2S supplementation through Erucin represents a promising alternative in MetS therapy, targeting smooth muscle cells and supporting the importance of lifestyle and nutrition in managing MetS.

Downregulation of inflammatory erectile dysfunction by Mantisa religiosa egg-cake through NO-cGMP-PKG dependent NF-kB signaling cascade activated by mixture of salt intake.

We hypothesized whether 10% praying-mantis-egg-cake (10% PMEC) can be applied against inflammatory-erectile-dysfunction and whether it could be linked to NO-cGMP-dependent PKG signaling cascade. Ninety male albino-rats were randomly distributed into nine (n = 10) groups. Group I was given distilled water. Group II and III were pre-treated with 80 mg/kg NaCl and 75 mg/kg MSG, respectively. Group IV was pre-treated with 80 mg/kg NaCl + 75 mg/kg MSG. Group V was administered with 80 mg/kg NaCl+ 3 mg/kg Amylopidin. Group VI was given 80 mg/kg NaCl + 10% PMEC. Group VII was treated with 75 mg/kg MSG + 10% PMEC. Group VIII was treated with 80 mg/kg NaCl+ 75 mg/kg MSG + 10% PMEC. Group IX was post-treated with 10% PMEC for 14 days. Penile PDE-51, arginase, ATP hydrolytic, cholinergic, dopaminergic (MAO-A) and adenosinergic (ADA) enzymes were hyperactive on intoxication with NaCl and MSG. The erectile dysfunction caused by inflammation was linked to alteration of NO-cGMP-dependent PKG signaling cascade via up-regulation of key cytokines and chemokine (MCP-1). These lesions were prohibited by protein-rich-cake (10% PMEC). Thus, protein-rich-cake (10% PMEC) by a factor of 4 (25%) inhibited penile cytokines/MCP-1 on exposure to mixture of salt-intake through NO-cGMP-PKG dependent-NF-KB signaling cascade in rats.

SPONTANEOUS TRANSVAGINAL INTESTINAL EVISCERATION IN AN ELDERLY WOMAN.

Introduction: Transvaginal intestinal evisceration is a rare surgical emergency that is associated with morbidity and mortality. Only a few cases of transvaginal evisceration have so far been described. The predisposing risk factors associated with this clinical condition are multifactorial. Case presentation: We report a case of an 85-year-old female that presented with spontaneous small bowel evisceration through the vagina. The loops of the small bowel appeared edematous and thickened but there was demonstrable visible peristalsis. She had no previous laparotomy or vaginal surgery. An emergency laparotomy was performed, and the small bowel was reduced into the abdomen through the vaginal defect. Afterward, a total abdominal hysterectomy was performed with the closure of the vaginal vault. The postoperative period was uneventful. Conclusion: The spontaneous evisceration of bowel loops can be successfully managed when patients with such cases present early and promptly managed. Prompt diagnosis and surgical management are crucial to prevent complications. If the eviscerated viscera are non-viable, resection and restoration of bowel continuity are imperative. Management should be individualized and multidisciplinary.

ACCIDENTAL INTRAOPERATIVE FINDING OF PARASITIC FIBROIDS IN THE MESENTERY OF A MIDDLE-AGED WOMAN.

Fibroid (myoma) is the most common benign tumor of the female genital tract. The tumour may occur in the uterine corpus as intramural, submucous, subserous, cervical fibroid; or in the broad ligament as intraligamentary fibroid or outside of uterus as parasitic fibroid. Parasitic fibroid is rare as a primary or secondary tumour. It is commonly diagnosed as an incidental finding during radiologic or abdominal surgical procedures. This was a case report of histologically confirmed multiple parasitic fibroids in a 39-year-old woman coexisting with primary uterine fibroids. The woman presented with a history of progressive abdominal swelling and associated lower abdominal pain of 8 years duration. There was an antecedent history of exploratory laparotomy with excision of uterine mass. Abdominal ultrasonography revealed multiple uterine fibroid nodules in the submucous, intramural and subserous layers of the uterus with bilateral normal ovaries. She had abdominal myomectomy. The intraoperative findings revealed multiple uterine fibroid nodules with a total weight of 1670g. There were multiple parasitic fibroid nodules attached to the serosa of the colon with the largest measuring 3.5 x 2cm. We discussed the management and associated challenges of unanticipated parasitic fibroids at surgery. We highlighted the role of multi-disciplinary care and advocated for a high index of suspicion while preparing for surgical intervention in women with multiple uterine fibroids.

Keratocystic odontogenic tumor: A biopsy service's experience with 104 solitary, multiple and recurrent lesions.

BACKGROUND: Keratocystic odontogenic tumor (KCOT) is a clinically significant cystic lesion of odontogenic origin. This study aimed to retrospectively review and describe the clinicopathologic features of KCOT and to objectively compare the clinical and histological features of solitary, multiple and recurrent KCOT in a Saudi Arabian population. MATERIAL AND METHODS: Biopsy request forms, pathology records and archival materials (all histological slides) of 104 cases of KCOT from 75 patients were retrieved. Demographic and clinical details as well as histological evaluation were analyzed and compared between the 3 groups using chi-squared or Mann-Whitney tests of association as appropriate. RESULTS: Significant differences were noted in the age of presentation, location and association with impaction between multiple and solitary cases. Histologically, there was a difference in the mitotic count, presence of satellite cysts and proliferating odontogenic epithelium between solitary and multiple lesions. There was no difference between the KCOT that later recurred and solitary lesion which did not recur even when matched clinically for age, sex and location. There were differences when solitary KCOT that later recurred or recurrent KCOT were compared with multiple lesions. Multiple lesions still had more significant proliferative activity parameters than solitary recurrence-related KCOT. CONCLUSIONS: KCOTs in Saudi Arabians are not different from those reported from other parts of the world. Clinical and histological analyses showed multiple KCOT is different from its solitary recurrent or non-recurrent counterparts and has a higher proliferative activity than both. Clinicohistologic features alone cannot wholly explain the behavior of KCOT.

Household survey on Human Papilloma Virus vaccine awareness among women of reproductive age in Ibadan, Nigeria.

BACKGROUND: Cervical cancer is the commonest female genital tract malignancy associated with high mortality in sub-Saharan Africa due to poor prevention plan. Human Papilloma Virus (HPV) is a necessary cause of cervical cancer, and the infection is vaccine preventable. Since the introduction of HPV vaccine, robust community surveys on awareness of the vaccine that capture end-users perspective is scarce. The aim of this study is to determine HPV vaccine awareness among women of reproductive age group. METHODS: This was a household survey that used multi-stage random sampling conducted amongst 1002 women aged 18-49 years from August to September 2012 in Mokola area, Ibadan, south western Nigeria. A self-administered pre-tested questionnaire was used for data collection. Descriptive, bivariate and multivariable analyses were performed, and statistical significance was set at 95% confidence level. RESULTS: The mean age was 29.8 +/- 8.2 years and 49.9% had female children. Only 4.6% had heard of HPV vaccine. A significantly higher odds of HPV vaccine awareness was found among highly skilled women, those initiating sexual intercourse at older ages; women with multiple sexual partners and those aware that cervical cancer is preventable. CONCLUSION: The awareness of HPV vaccine is low. Policies and programs that will improve awareness utilising culturally sensitive messages are imperative.

A simple novel prognostic model for early stage oral tongue cancer.

The prognostication of patient outcome is one of the greatest challenges in the management of early stage oral tongue squamous cell carcinoma (OTSCC). This study introduces a simple histopathological model for the prognostication of survival in patients with early OTSCC. A total of 311 cases (from Finland and Brazil) with clinically evaluated early stage OTSCC (cT1-T2cN0cM0) were included in this multicentre retrospective study. Tumour budding (B) and depth of invasion (D) were scored on haematoxylin-eosin-stained cancer slides. The cut-off point for tumour budding was set at 5 buds (low <5; high ≥5) and for depth of invasion at 4mm (low <4mm; high ≥4mm). The scores of B and D were combined into one model: the BD predictive model. On multivariate analysis, a high risk score (BD score 2) correlated significantly with loco-regional recurrence (P=0.033) and death due to OTSCC (P<0.001) in early stage OTSCC. The new BD model is a promising prognostic tool to identify those patients with aggressive cases of early stage OTSCC who might benefit from multimodality treatment.

Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia.

Thrombopoietin receptor agonists (TPO-RA) have recently been introduced for the treatment of immune thrombocytopenia (ITP), an anti-platelet-antibodies autoimmune disease. The observation of a low frequency of bleeding episodes despite their thrombocytopenia suggests the existence of a compensatory mechanism. This study aimed to evaluate the effect of TPO-RA treatment on platelet function and on the procoagulant state in ITP patients before (ITP-bR) and after responding (ITP-aR) to treatment. Plasma- and microparticle (MP)-associated procoagulant capacity from ITP patients was similar before and after responding to the TPO-RA regimen but higher than the healthy control values. High MP-associated procoagulant activity did not seem to be due to increased platelet activation, since platelet stimulation by agonists was reduced in ITP-bR and ITP-aR patients. It could be related to increased platelet apoptosis, evaluated in terms of surface phosphatidylserine (PS), observed in both ITP groups. In summary, TPO-RA treatment increased platelet count but did not ameliorate their function and did not change plasma- and MP-associated procoagulant state of ITP patient responders to this therapy.

Vesico-vaginal fistula repair as a day case: is it a worthy venture?

Two vesico-vaginal fistula patients who were successfully managed with outpatient care as an alternative approach, to ensure early access to care and integration into their family. The two patients had simple uncomplicated mid-vagina fistulae surgically repaired with local infiltrative anaesthesia. We suggest some selection criteria and clinical guidelines that can facilitate successful treatment by this choice of care.

Platelet apoptosis and agonist-mediated activation in myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) have a defect in the differentiation of bone marrow multipotent progenitor cells. Thrombocytopenia in MDS patients may be due to premature megakaryocyte death, but platelet apoptotic mechanisms may also occur. This study aimed to study function and apoptotic state of platelets from MDS patients with different platelet count. Reticulated platelets, platelet activation, activated caspases and annexin-V binding were evaluated by flow cytometry. Pro-apoptotic Bax and Bak proteins were determined by western blots and plasma thrombopoietin by ELISA. Microparticle-associated procoagulant activity and thrombin generation capacity of plasma were determined by an activity kit and calibrated automated thrombography, respectively. High plasma thrombopoietin levels and low immature circulating platelet count showed a pattern of hypoplastic thrombocytopenia in MDS patients. Platelets from MDS patients showed reduced activation capacity and more apoptosis signs than controls. Patients with the lowest platelet count showed less platelet activation and the highest extent of platelet apoptosis. On this basis, patients with thrombocytopenia should suffer more haemorrhagic episodes than is actually observed. Consequently, we tested whether there were some compensatory mechanisms to counteract their expected bleeding tendency. Microparticle-associated procoagulant activity was enhanced in MDS patients with thrombocytopenia, whereas their plasma thrombin generation capacity was similar to control group. This research shows a hypoplastic thrombocytopenia that platelets from MDS patients possess an impaired ability to be stimulated and more apoptosis markers than those from healthy controls, indicating that MDS is a stem cell disorder, and then, both number and function of progeny cells, might be affected.

Metachronus endometrial carcinoma in a seventy five year old woman with carcinoma of the left breast treated with tamoxifen.

BACKGROUND: A second cancer is a different type of cancer than the original cancer. It is diagnosed after a completed treatment for the first cancer. Second cancers occur in only one to three percent of survivors. The level of risk is very small. In general, greater numbers of cancer survivors are living longer due to improvements in treatment. Whether or not a second cancer develops is dependent on many factors. These include the age of the patient when treated, the treatment received, the genetic make-up and family history. The actual number of people who will get a second cancer is relatively small. Each cancer survivor's experience is unique. The aim of this report is to call attention to what might be an emerging place of secondary malignancies in cancer survivors in our setting. METHOD: We report a case seen in our practice of a seventy five year old woman who was treated for invasive ductal carcinoma of the left breast and developed invasive endometrial carcinoma about 4 years later. CONCLUSION: There is a need to be on the lookout for possible second malignancies in cancer survivors. Examination and tests for second malignancies should be part of the routine follow up procedures in this group of patients.

[Calcific uremic arteriolopathy. a case report and review of the literature]. / Arteriolopatía cálcica urémica: comunicación de un caso y revisión de la literatura.

BACKGROUND: Calcific uremic arteriolopathy is defined as a syndrome consisting of ischemic skin ulceration due to calcification of the wall of the arterioles of the subcutaneous tissue as a result of hyperparathyroidism in uremic patients. CASE REPORT: A 55-year old female patient, hypertense, with heart failure and kidney failure treated with hemodialysis, who presented lower limb pain and hypercalcemia. On physical examination, skin lesions with symmetrical peripheral pulses present in the limbs. Laboratory tests revealed hypercalcemia, hyperphosphatemia, and very high parathyroid hormone levels. Parathyroidectomy was performed and biopsy of skin lesions, the patient having a torpid course causing exitus. Autopsy was performed, with histologic features characteristic of calcific uremic arteriolopathy. CONCLUSIONS: Calcific calcium uremic arteriolopathy or calciphylaxis is a complex and variable disease that is difficult to diagnose and whose treatment is complicated. Despite the efforts of the investigators, there are still many questions regarding its pathogenesis. This acts as an incentive for further research to establish the most appropriate actions to take to maintain an adequate quality of life for the patients and avoid complications that trigger death in some cases.

Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

Autoimmune T cell responses directed against insulin-producing ß cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials.

The learning curve of radical hysterectomy for early cervical carcinoma.

Cervical cancer remains a public health concern in developing countries that lack the wherewithal to cope with the associated challenges. Screening for premalignant cervical lesions and offering definitive care for early disease is the key to preventing the scourge. We conducted an audit of the radical hysterectomies performed on account of early cervical carcinoma at our centre between September 2006 and August 2008, following capacity-building by Operation Stop Cervical Cancer. Ten women aged 35 to 60 years were managed. All had type III radical hysterectomy. Three patients had adjuvant teletherapy (one was stage IIb, diagnosed intra-operatively). There was a linear reduction in the surgical blood loss and duration of surgery. Average blood loss was 1500 mls; four had blood transfusions. One case was complicated with rectovaginal fistula (the woman with stage IIb disease) and another had bilateral lymphoedema and left lower limb sensory neuropathy. There was no tumour recurrence on follow-up. Definitive surgery for early cervical cancer is feasible in developing countries despite limited resources. Audit of surgical care of cervical cancer will assist in strengthening the scarce skill. Determination of suitable cases during preoperative evaluation is crucial to the success of the surgery.

Determinants of post-caesarean wound infection at the University College Hospital Ibadan Nigeria.

OBJECTIVE: To determine the risk factors that predispose patients to post-caesarean wound infection at a tertiary health institution in developing country. METHOD: It was an observational study of all women that had caesarean (elective and emergency) delivery between July and September, 2004. The outcome of their post-caesarean wound was assessed. Statistical analysis (Bivariate and logistic regression) of the identified risk factors in patients who developed wound infection was performed at a 95% level of confidence. RESULTS: The post-caesarean wound infection rate was 16.2%. The identified risk factors were lower educational status, multiple pelvic examination, offensive liquor at surgery and patients that are unbooked. Following logistic regression, women with up to primary school were 20 times more likely than those with secondary education and above to develop wound infection (95% CI OR = 1.8 to 250.0). CONCLUSION: The outcome showed that the identified determinants of post-caesarean wound infection were comparable with earlier reports. Women with lower educational status are more at risk in this study. Therefore, these women need special attention to reduce the risk.

[Fibrate-induced deterioration of renal function]. / Deterioro de la función renal inducido por fibratos.

INTRODUCTION: Fibrates represent one of the medications used to treat patients with hyperlipemia. Deterioration in renal function is not a very known adverse effect of fibric acid derivates. In the last 26 months we have detected thirteen patients with acute renal failure associated to fibrates in our outpatients' clinic. SUBJECTS AND METHODS: The aim of our study is to analyze our experience in deterioration in renal function associated to fibrates use. This is a retrospective charts review. RESULTS: From the thirteen patients (8 males/5 females) with mean age of 65.5 +/- 12.2 years, ten received Fenofibrate (FN), one Bezafibrate (BZ) and two Gemfibrozil (GF). Six cases had previously normal renal function and the seven remaining had mild chronic renal failure (CRF). The increase of serum Creatinine (Crs) value was higher than 74%. Acute renal failure was reversible in 9 patients (group 1), but the other 4 did not recover their previous renal function (group 2). The average of Crs before fibrate treatment was 1.33 +/- 0.36 mg/dl (Creatinine clearance 63.2 +/- 26.6 ml/min) and the highest average of Crs during the treatment was 2.22 +/- 0.49 mg/d (Creatinine clearance 37.3 +/- 11.9 ml/min). The average time until acute renal failure diagnosis was 6.7 +/- 5.8 months and the recovery of renal function was delayed an average of 3.8 +/- 3.5 months after fibrates withdrawn. Group 2 patients had a higuer Crs and longer time with fibrates than group 1 patients. CPK values were normal in all cases. In two patients renal biopsy was performed and no significant lesions were detected. CONCLUSION: The fibrate treatment can induce an acute renal failure. Four patients (30.8%) did not recover their basal renal function. When fibrate treatment begins a renal function should be monitored specially in patients with CRF.

Alpha-smooth muscle actin within epithelial islands is predictive of ameloblastic carcinoma.

Ameloblastoma is the most common clinically significant odontogenic tumor. It is considered benign but locally invasive and associated with variable clinico-pathological behavior. Ameloblastic carcinoma is a malignant tumor having features of ameloblastoma in addition to cytologic atypia with or without metastasis. It is aggressive and associated with poor prognosis. The aim of this study was to examine which epithelial and stromal markers are predictive of histologically diagnosed ameloblastic carcinoma and can sufficiently differentiate it from solid/multicystic ameloblastoma (SA). We examined immunohistochemically Ki-67, epithelial membrane antigen (EMA), alpha-smooth muscle actin (alpha-SMA), calponin, p63 and DNA content using image (ICM) and flow cytometry (FCM) in three ameloblastic carcinomas and up to 18 SAs. The important findings were that Ki-67 labeling index was significantly higher in ameloblastic carcinoma than SA while EMA, calponin, p63, ICM and FCM did not sufficiently differentiate the two groups of lesions. Expression of alpha-SMA was consistently obtained within the epithelial island cells of ameloblastic carcinoma and not in SA, although the marker was well expressed in the stroma of both lesions. We therefore conclude that the presence of alpha-SMA within the epithelial islands is highly predictive of ameloblastic carcinoma.

Ascorbic acid and the effect of cigarette smoke on tissues--a preliminary report.

BACKGROUND: Smoke from the average cigarette contains chemicals, which are highly toxic, causing chronic airways diseases in smokers as well as non-smokers exposed to environmental tobacco smoke (ETS). It is associated with an increased risk of developing asthma, pneumonia, bronchitis and cancer. OBJECTIVE: To investigate the effect of ascorbic acid on the degenerative effect of passive cigarette smoke on some vital organs. METHODS: A total of 16 male rabbits divided into four groups (A, B, C, D) of 4 rabbits each, were used. Group A rabbits were exposed to passive cigarette smoke for 45-60 minutes daily; group B was treated similarly but also had 5 mg/g body weight of ascorbic acid daily. Group C had ascorbic acid only and Group D was the untreated control group. After six weeks of the above treatment, the animals were sacrificed for histological investigation of some of their vital organs. RESULTS: Tobacco smoke had deleterious effects on the lungs, testes and kidneys; no significant changes were seen in the liver, brain and.heart. Ascorbic acid appeared to have some attenuating effect on inflammatory processes as observed in the lungs. Varying degrees of hypospermatogenesis were observed in the seminiferous tubules while the epididymis contained no spermatocytes in both groups A and B. CONCLUSION: Ascorbic acid has some attenuating effect on inflammatory processes but it neither stops inflammation (as seen in the lungs) nor declining function (as signified by hypospermatogenesis in the testes). Therefore, it is doubtful that the long-term effects of tobacco smoke can be prevented by the use of ascorbic acid.

One-stage repair for combined fistulas: myth or reality?

OBJECTIVE: The repair of combined vesico-vaginal fistulas (VVFs) and recto-vaginal fistulas (RVFs) is challenging to both surgeon and patient. The multistage approach involves at least 3 surgical sessions, all associated with morbidity and sometimes with a colostomy procedure as well. The outcomes of the 1-stage approach were examined. METHODS: Twenty patients aged between 16 and 38 years were recruited for a multicenter study conducted from March 2005 to August 2006. Prolonged obstructed labor was the cause of all fistulas. The VVFs were mainly midvaginal (60%), juxtaurethral (25%), and juxtacervical (15%). The RVFs measured between 1 and 3 cm, they were low in 70% of cases, and 1 was associated with fourth-degree perineal tear. Bowel preparation was performed in all patients prior to surgery. No patient underwent temporary colostomy. RESULTS: Both VVFs and VVFs were successfully closed in all patients, as evidenced by the continence dye test. CONCLUSION: The combined repair relieves economic constraints and emotional challenges, and it accelerates restoration to health and social reintegration for women affected with both VVFs and RVFs.