Effect of dapagliflozin against NAFLD and dyslipidemia in type 2 diabetic albino rats: possible underlying mechanisms.

OBJECTIVE: The aim was to investigate the effect of dapagliflozin on non-alcoholic fatty liver disease and dyslipidemia in type 2 diabetic rats by studying the histopathological structure of the liver and detecting possible underlying mechanisms for this impact by evaluating the potential anti-inflammatory action of dapagliflozin. MATERIALS AND METHODS: 100 albino rats were used in this work and divided into five equal groups: group I (Control group), group II (Control diabetic group), group III (was administered dapagliflozin, 0.75 mg/kg, p.o.), group IV (was administered dapagliflozin, 1.5 mg/kg, p.o.), and group V (was administered dapagliflozin, 3 mg/kg, p.o.). RESULTS: In our study, the total body weight, liver weight, liver index, blood glucose level, insulin level, insulin resistance, total cholesterol, triglycerides, liver enzymes, IL-1 ß, and MDA were significantly higher in the control diabetic group than the normal group. The dapagliflozin reduced all the above variables significantly in a dose-dependent manner compared to the control diabetic group (p-value = 0.001 for all). CONCLUSIONS: Dapagliflozin may be a promising novel treatment strategy for treating T2DM-related non-alcoholic fatty liver disease (NAFLD), and dyslipidemia where it possesses anti-oxidative, anti-inflammatory and anti-dyslipidemic effects.

[Evolution and progress of lung transplantation: An analysis of a cohort of 600 lung transplant patients at the Hospital Foch]. / Évolution et progrès en transplantation pulmonaire : étude de la cohorte de 600 premiers patients transplantés pulmonaires à l'hôpital Foch.

Lung transplantation is deemed to be the only effective therapy that improves survival for patients with end stage lung disease. The aim of our study was to examine the progress achieved over the last two decades and to demonstrate the effectiveness and safety of this treatment. METHODS: A retrospective analysis of a cohort of 600 consecutive lung transplant patients treated at the hospital Foch (Suresnes, France) between 1988 and 2014. They were split into three groups of 200 patients each: 1988-2004, 2004-2011, 2011-2014. RESULTS: Time and mortality on waiting list, perioperative mortality, the incidence of acute rejection in the first year and chronic lung allograft dysfunction (CLAD) at 5 years posttransplantation, have all decreased. Global survival at 1 and 5 years for the 600 patients increased from 78% and 57% to 86% and 75% respectively for the 200 last patients. Patients with cystic fibrosis have a better 5 year survival than those with emphysema or pulmonary fibrosis (68% vs. 54 % for emphysema and 37% for fibrosis). For the last 200 patients, 5 year survival is 81% for CF patients, 78 % for emphysema and 47% for fibrosis. Emergency transplantation had a 60% 5 years survival. Proliferative complications, arterial hypertension and renal function impairment are being monitored long term. CONCLUSION: The twenty-five years experience shows a consistent improvement in the results of lung transplantation which is now accepted as the only effective curative treatment for end stage lung disease.

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics.

In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.

New polyhydroxylated sterols from Palythoa tuberculosa and their apoptotic activity in cancer cells.

The chemical study on the total extract of the zoanthid Palythoa tuberculosa, collected from the Red Sea, resulted in the isolation of seven polyhydroxylated sterols (1-7), six of which, palysterols A-F (2-7), are new. Their chemical structures were elucidated on the basis of extensive analysis of their 1-, 2D NMR and MS spectroscopic data. This is the first chemical investigation on the species collected from Red Sea. We studied the cytotoxic effects of the total extract and some of the new polyhydroxylated sterols in three human cancer cell lines (MCF-7, HeLa, and HT-29) and one non-cancerous human cell line (KMST-6). Palysterol F (7), in particular, was able to selectively induce high levels of apoptosis (>75%) in breast adenocarcinoma (MCF-7) cells but not HeLa, HT-29 and KMST-6 cells.

Bioactive terpenoids from the Red Sea soft coral Sinularia polydactyla.

Chemical investigation of an ethyl acetate soluble fraction of Sinularia polydactyla (Ehrenberg) led to the isolation of three known terpenoides, two of them sterols, 24-methylcholestane-3ß,5α,6ß,25-tetrol 25-monoacetate (1), 24-methylcholestane-5-en-3ß,25-diol (2), in addition to a cembranoid diterpene, durumolide C (3), for the first time. The cytotoxicity and antimicrobial activities of the ethyl acetate extract and the isolated compounds 1-3 were evaluated in vitro. Durumolide C (3) showed selective cytotoxicity against HepG2 (IC50 1.0 µg/mL), whereas 24-methylcholestane-3ß,5α,6ß,25-tetrol 25-monoacetate (1) showed IC50 of 6.1 and 8.2 µg/mL against Hep2 and HCT human cancer cell lines, respectively.

The prenatal toxic effect of methylmercury on the development of the appendicular skeleton of rat fetuses and the protective role of vitamin E.

Methylmercury (MeHg) is an environmental contaminant that is found in many ecosystems. Many studies reported that MeHg toxicity is accompanied by increased lipid peroxidation that may lead to oxidative damage to DNA, RNA, and proteins. Vitamin E is considered as the most effective antioxidant preventing lipid peroxidation. The aim of this study was to evaluate the effects of MeHg exposure during pregnancy on the development of the appendicular skeleton in rat fetuses and whether vitamin E administration could reduce this toxicity. Positively mated adult female Sprague-Dawley rats were used and divided into the following experimental groups: control group, received only deionized water, and four MeHg treated groups received 1 mg of MeHg/kg/d, 2 mg of MeHg/kg/d, 1 mg of MeHg/kg/d plus 150 mg of vitamin E/kg/d, and 2 mg of MeHg/kg/d, plus 150 mg of vitamin E/kg/d starting from Day 0 of gestation. On Day 20 of gestation, the fetuses from the pregnant rats were extracted and the fetal growth parameters were evaluated. Skeletal evaluation of ossification of both fore- and hind-limbs, and coxal bones were undertaken. Results showed that treatment with MeHg caused adverse effects on fetal growth parameters and ossification of the bones. The coadministration of vitamin E with MeHg revealed an improvement in these parameters. These results suggest that vitamin E may ameliorate some aspects of MeHg developmental toxicity. The underlying and human health implications warrant further investigations.

Pulmonary arterial hypertension masquerading as severe refractory asthma.

Once the diagnosis of pulmonary arterial hypertension is established, wheezing and chronic cough are rarely described during the course of the disease. The present study reports on two nonsmoking patients with severe pulmonary arterial hypertension, confirmed by right-heart catheterisation, who developed chronic cough, wheezing and irreversible obstructive lung disease masquerading as adult-onset severe refractory asthma. In both cases, extrinsic proximal airway obstruction by dilated pulmonary arteries was demonstrated by fibreoptic bronchoscopy and computed tomography of the chest. The present observations add dilatation of the central pulmonary arteries with compression of the mainstem bronchi to the list of masqueraders of asthma in patients with pulmonary arterial hypertension.

Recurrence of prolactin-producing endometrial stromal sarcoma with sex-cord stromal component treated with progestin and aromatase inhibitor.

INTRODUCTION: Endometrial stromal tumors with sex-cord-like elements are relatively rare. We report a case of this neoplasm with prolactin as a tumor marker for recurrent disease. We also report response of recurrent disease to progesterone and aromatase inhibitor. CASE REPORT: A 48-year-old woman was diagnosed with Stage I endometrial stroma sarcoma with sex-cord component at the time of hysterectomy for presumed fibroid uterus. One and a half years later, she presented with recurrent disease in the abdomen associated with breast tenderness, galactorrhea, and an elevated prolactin level. She received three cycles of BEP (Bleomycin, Etoposide, Cisplatin) with partial response and followed by an optimal debulking procedure. Two out of a six additional planned cycles of BEP were administered with complete tumor response and normalized prolactin level. Second recurrence, 9 months later, again presented with galactorrhea and rising prolactin. Disease was progressive through three cycles of Docetaxel and Gemcitabine therapy, but had an objective response to treatment with anastrozole and megestrol acetate. Prolactin level normalized. Two years later there is stable disease and the patient remains symptom-free. DISCUSSION: Endometrial stromal sarcoma with sex-cord stromal component may be hormonally functional. Similarly to pure endometrial stromal sarcomas, they may respond to hormonal treatment, and further study is warranted.

Comparative pharmacokinetics of diphenhydramine in camels and horses after intravenous administration.

The pharmacokinetics of diphenhydramine (DPHM) was compared in camels (n = 8) and horses (n = 6) following intravenous (i.v.) administration of a dose of 0.625 mg/kg body weight. In addition, the metabolism and urinary detection time of DPHM was evaluated in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows. The terminal elimination half lives (h) were 1.58 (1.13-2.58) and 6.11 (4.80-14.1), and the total body clearances (L/h per kg) were 1.42 (1.13-1.74) and 0.79 (0.66-0.90). The volumes of distribution at steady state (L/kg) were 2.38 (1.58-4.43) and 5.98 (4.60-8.31) and the volumes of the central compartment of the two compartment pharmacokinetic model were 1.58 (0.80-2.54) and 2.48 (1.79-3.17). All the pharmacokinetic parameters in camels were significantly different from those of horses. Five metabolites of DPHM were tentatively identified in the camel's urine. Two metabolites, diphenylmethoxyacetic acid and 1-(4-hydroxyphenyl)-phenylmethoxyacetic acid, were present in the acid fraction. Two metabolites, desamino-DPHM and diphenylmethanol, were identified in the basic fraction, in addition to DPHM itself, which was present mainly as a conjugate. Even after enzymatic hydrolysis, DPHM could be detected for up to 24 h in camels after an i.v. dose of 0.625 mg/kg body weight.

Comparative disposition of tripelennamine in horses and camels after intravenous administration.

The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, the volumes of the central compartment of the two compartment pharmacokinetic model were 1.75 (0.68-2.27) and 1.06 (0.91-2.20) L/kg. There was no significant difference (Mann-Whitney) in any parameter between camels and horses. The extent of protein binding (mean +/- SEM) 73.6 + 8.5 and 83.4 +/- 3.6% for horses and camels, respectively, was not significantly statistically different (t-test). Three metabolites of T were identified in urine samples of camels. The first one resulted from N-depyridination of T, with a molecular ion of m/z 178, and was exclusively eliminated in conjugate form. This metabolite was not detected after 6 h of T administration. The second metabolite, resulted from pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detected in urine sample for up to 12 h after T administration. The third metabolite has a suspected molecular ion of m/z 285, was eliminated exclusively in conjugate form and could be detected for up to 24 h following T administration. T itself could be detected for up to 27 h after i.v. administration, with about 90% of eliminated T being in the conjugated form.

Bilateral renal cancer in children: a difficult, challenging and changing management problem.

Bilateral disease occurs in 6% of patients with Wilms' tumour. Bilateral renal involvement is present in 25%-50% of children with B-cell non-Hodgkin's lymphoma. Paediatric oncologists therefore encounter bilateral renal disease relatively frequently. A patient with bilateral Wilms' tumour is presented, in whom at least 16 synchronous tumours in the kidneys were treated successfully by primary chemotherapy and 'nephron-sparing' surgery, without renal radiotherapy. We believe the successful treatment without radiotherapy will allow greater potential for normal growth in the future. The case history of a patient with renal failure due to the infiltration of both kidneys by lymphoma and who was treated successfully by chemotherapy, is also presented. One kidney has completely returned to normal function and growth; the other has completely failed and almost disappeared, demonstrating complete reversibility of the damage up to some critical point, beyond which, failure and atrophy result. These two case histories demonstrate extreme examples of clinical dilemmas involving bilateral renal tumours and allow discussion of modern management aimed at preserving renal function.

Adenocarcinoma of the ileum with an enterotubal fistula presenting as an adnexal mass.

Small bowel adenocarcinomas account for 3% of gastrointestinal malignancies, and 20 to 25% of these arise in the ileum. Clinical presentation is variable, and early diagnosis is difficult. A 56-year-old postmenopausal woman presented with crampy abdominal pain, anorexia, and weight loss. Pelvic examination and ultrasound revealed a 6 x 8-cm complex right adnexal mass. At laparotomy, en bloc resection of the right adnexa and the densely adherent ileal segment was performed along with a hysterectomy and a left salpingo-oophorectomy. The final pathology showed a moderately differentiated invasive adenocarcinoma of the ileum with a malignant enterotubal fistula. This is the first case reported in the literature of an ileal adenocarcinoma with a tubal fistula masquerading as an adnexal mass.

High levels of CA-125 in a case of a parasitic leiomyoma presenting as an abdominal mass.

A 32-year-old woman presented with increasing abdominal girth and discomfort secondary to a 18-week-size mass and a CA-125 level of 1539. She underwent an exploratory laparotomy and resection of a parasitic fibroid following which the CA-125 levels decreased and normalized within a month. A review of English literature indicates that association of raised CA-125 levels with fibroids is inconsistent and very modest and such high levels have not been previously reported.

Mucinous adenocarcinomas of the vulva.

An 80-year-old nullipara had a 2.0-cm cystic tumor of the right labium majus. Histologic diagnosis was mucinous eccrine carcinoma. Seventy-five percent of these rare skin adnexal tumors arise on the face, eyelid, or scalp; but none has been reported on the vulva. Indolent localized growth is usual with regional nodal spread in 11% and distant metastases in 3%. A 67-year-old multipara had a 1.2-cm polypoidal nodule of the posterior fourchette. Histologically, a colonic type mucinous carcinoma was arising within a villous adenoma. Mucicarmine and CEA stains were positive. Extensive workup failed to reveal other primary cancers in either patient. Both patients are well 19 and 17 months after radical vulvectomies and node-negative groin dissections. These cases illustrate further the diversity in cell type and biologic behavior of vulvar adenocarcinomas.

Teenage pregnancy: are teenagers a high risk group?

OBJECTIVES: To study health profile of pregnant teenagers and their pattern of utilization of primary health care services in comparison with pregnant women aged 20-35 years in Abha, Saudi Arabia. STUDY DESIGN: A cohort of 1938 Saudi pregnant women (214 teenagers less than 20 years and 1724 aged 20-35 years) was selected by stratified random sampling technique. They were screened for anemia and hypertension using WHO criteria and followed until delivery to observe the method of delivery. RESULTS: The prevalence of anemia (9.6% and 12.0%, respectively) and hypertension (1.1% and 3.5%, respectively) was not significantly different among primigravida of both age groups. The same trend was observed among multigravida. Follow-up showed that the rate of abnormal deliveries among primigravida of both groups was not significantly different, and even lower among multigravida teenagers. Pregnant women in both groups had similar average prenatal visits (6.6 +/- 1.1 and 6.7 +/- 1.2 respectively, P < 0.05) and the majority contacted the primary health care center early in pregnancy (87.4% and 88.9%, respectively, P < 0.05). CONCLUSION: These results indicate that pregnant teenagers are not a high risk group if good prenatal care is provided.

PIP: Teenage pregnancy has been shown to be associated with an increase in obstetric complications. In particular, gestation associated hypertension and anemia were found more frequently among these young women. The authors screened 1938 pregnant Saudi women for anemia and hypertension using WHO criteria and followed them until delivery to observe the method of delivery in the study of whether or not pregnant women younger than 20 years old are at greater risk of obstetric complications than pregnant women aged 20-35 years. The women were selected by stratified random sampling technique from Abha, Saudi Arabia. 214 were younger than 20 years old, while the rest were aged 20-35. Among primigravida pregnant women younger than 20 years old, 9.6% were anemic and 1.1% suffered hypertension. Among primigravida pregnant women aged 20-35 years old, 12.0% were anemic and 3.5% suffered hypertension. These differences in rates between age groups are not significant. The same trend was observed for multigravida women. Furthermore, the rate of abnormal deliveries among primigravida of both groups was not significantly different, and even lower among multigravida teens. Pregnant women in both age groups made, on average, 6.6-6.8 prenatal visits, while 87.4% and 88.9%, respectively, contacted the primary health care center early in pregnancy. It may be concluded from these findings that pregnant teens do not constitute a high-risk group if good prenatal care is provided.

Glomus tympanicum chemodectoma: unusual radiological findings.

A 64-year-old Qatari female, with a one-year history of right otorrhoea and deafness, had a reddish-white mass projecting into the right ear canal, through the tympanic membrane, that proved histopathologically to be a paraganglioma. Computerized tomography (CT) of the temporal bones showed extensive destruction of the right mastoid bone, the posterior ear canal wall, and the sinus plate, with total disruption of the ossicles, simulating a malignant tumour, which is unusual for a middle ear paraganglioma.

Granular cell tumour of the larynx in an eight-year-old girl.

Granular cell tumour is a rare benign neoplasm, that can affect many parts of the body, as single or multiple lesions. It is more common in black people and females. Typically it occurs between the fourth and fifth decades of life, with the median age for the laryngeal variety as 36 years. About 30 to 50 per cent occur in the tongue and 30 per cent in the skin. A case of granular cell tumour of the larynx is reported in an eight-year-old girl, presenting with hoarseness of voice. She was successfully treated with local excision of the tumour. This tumour is rare in the larynx where it is more common in males than females although granular cell tumours are found more frequently in females generally. For these reasons the authors suspect that their case, of a laryngeal granular cell tumour occurring in an eight-year-old girl might be the youngest to be reported.

An epidemiologic study of primary health care service utilization of summer visitors to Abha, Asir, Saudi Arabia.

Primary health care (PHC) service utilization by summer visitors to Abha, Saudi Arabia was studied among 227 families including 1443 persons attending the Al-Manhal Primary Health Care Center (PHCC) during August 1991. Summer visitors added an excess load on PHC services: 1.8% for preventive activities, 3.3% for diagnostic activities and 17.4% for curative activities. A significant excess of utilization of curative PHC activities was observed among summer visitors compared to residents. On the other hand, a significant decrease in utilization of preventive and diagnostic PHC services was noted among summer visitors. This study demonstrates the importance of augmenting PHCCs with staff and supplies in residential areas during the summer to cope with the situation and of providing proper and adequate PHC services. More health education is needed to inform people about importance of preventive PHC for better utilization of the available services.

Preparing the young to look after the old.

In Malaysia the steady rise in the proportion of people aged 60 or more, and an awareness of their complex psychosocial, economic and health care needs, have led medical faculties to introduce geriatrics as an essential subject in their curricula. The efforts made in this field by the School of Medical Sciences of the Universiti Sains Malaysia are outlined in the present article.