Immunohistochemical assessment of endothelin-1 axis in psoriasis, basal cell carcinoma and squamous cell carcinoma.

AIM: Endothelin-1 is an autocrine growth factor for keratinocytes, an effect controlled by its A and B receptors, with no previous comparison of endothelin axis expression in inflammatory and neoplastic skin diseases showing keratinocyte proliferation. The aim of the study was to investigate endothelin-1 axis expression in skin lesions of psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). METHODS: This study included 40 subjects (8 patients with SCC, 12 patients with BCC, 10 patients with psoriasis, and 10 healthy controls). Biopsies from lesional skin of patients and normal skin of controls were examined immunohistochemically for endothelin-1 and its receptors A and B frequency and grade of expression. RESULTS: Endothelin-1 and receptor A were detected in all patients with SCC and psoriasis, with a higher frequency and grade of expression than controls and BCC. The frequency of receptor B expression was significantly lower while higher staining grade was found in BCC (8.3%) rather than other studied groups. CONCLUSION: A comparable higher frequency and grade of expression of endothelin-1 and its receptor A are documented in psoriasis and SCC than in BCC and controls denoting their involvement in keratinocyte proliferation in both diseases. Receptor A is the predominately expressed receptor in psoriasis and SCC.

Can laparoscopic removal of Essure device before embryo transfer correct poor reproductive outcome pattern in IVF? A case report.

OBJECTIVE: This report describes a successful surgical approach to multiple in vitro fertilization (IVF) failures in the setting of hydrosalpinges, which had been previously treated with Essure inserts. MATERIALS AND METHODS: A non-smoking 33-year-old Caucasian G2 P0020 (body mass index: BMI = 22) attended for second opinion. Her history was significant for bilateral hydrosalpinges having been noted on hysterosalpingogram two years earlier. This was managed by hysteroscopic placement of Essure inserts bilaterally. One year later, and now with Essure in situ, the patient completed three IVF cycles elsewhere. Her first and third IVF attempts resulted in biochemical pregnancy, while human chorionic gonadotropin (hCG) was negative after the second cycle. Upon presentation at the authors' center and before beginning a fourth IVF cycle, further testing and surgical removal of the Essure devices was recommended. RESULTS: Repeat hysteroscopy was unremarkable; laparoscopic bilateral salpingectomy and extirpation of Essure implants was accomplished without difficulty. Following menses, the patient initiated IVF with three embryos transferred. At day 60, a single intrauterine pregnancy was identified with positive cardiac activity (rate > 100/min). Her obstetrical course was uneventful; a healthy 4,195 gram male infant was delivered (breech) by Cesarean at 40 weeks' gestation. CONCLUSION: Essure inserts comprise inner fibers of polyethylene terephthalate, a stainless steel coil, and a nickel-titanium coil. The product received FDA approval as a contraceptive in 2002 although its use for hydrosalpinx remains off-label. While successful outcomes with IVF following Essure placement have been reported, this is the first description of pregnancy and delivery from IVF after Essure removal. Essure may be considered for sterilization when laparoscopy is contraindicated, but experience with its use specifically for treating hydrosalpinges before IVF is limited. This observed association between prior poor IVF outcomes and Essure with subsequent delivery after surgical Essure removal is the first of its kind to be reported, and warrants further investigation.

Oral sildenafil citrate: a potential approach for improvement of endometrial thickness and treatment of unexplained infertility in women.

OBJECTIVE: The study aimed to determine the impact of using sildenafil citrate as an adjuvant with clomiphene citrate (CC) in the treatment of women with unexplained infertility. PATIENTS AND METHODS: 130 women with unexplained infertility were enrolled in a prospective randomized study. After dividing into two groups, all patients received CC 50 mg-BD from the 2nd to the 7th day of the cycle. Oral sildenafil citrate 20 mg was given BD to the study group from the end of menstruation till ovulation. A transvaginal ultrasound was carried out for all patients to assess ovulation, number of follicles, and endometrial thickness (ET). The beta-hCG blood test was used to determine pregnancy two weeks after ovulation followed by an ultrasound to confirm viability. Adverse effects were recorded and miscarriage, ectopic, and multi-fetal pregnancy were followed up for twelve weeks. RESULTS: Median ET in the study group was 8 mm compared to 7 mm in the control group (p<0.01). The number of pregnancies increased in the study group but with no significant difference. The median ET was greater in the study group with an infertility duration of less than 2 years. Headache was the most significant adverse effect in the study group (9.2% vs. 1.5%, p=0.052). CONCLUSIONS: Adding sildenafil citrate to CC is a good choice for overcoming the antiestrogenic action of CC and improving ET in women with unexplained infertility, especially in those with less than 2 years of infertility.

Evaluation of zinc level in skin of patients with necrolytic acral erythema.

BACKGROUND: Necrolytic acral erythema (NAE) is considered a cutaneous sign of hepatitis C virus infection. Its exact pathogenesis is still not fully understood, with some reports about decreased serum zinc levels but none about its level in the skin. OBJECTIVES: To assess skin (lesional and perilesional) and serum zinc levels in patients with NAE and compare them with levels in control subjects. METHODS: Fifteen patients with NAE and 10 healthy controls were included in this study. Assessment of zinc level, in serum by graphite furnace atomic absorption spectrophotometry and in lesional and perilesional skin biopsies by flame atomic absorption spectrometry, was done in all subjects. Re-evaluation of serum and lesional skin zinc level was done after oral zinc treatment. RESULTS: Mean±SD zinc levels were significantly lower in patients (serum 0·44 ± 0·13 mg L(-1) ; lesional skin 42·6 ± 18·9 mg L(-1) ; perilesional skin 32·5 ± 17·2 mg L(-1) ) than controls (serum 1·17 ± 0·29 mg L(-1) ; skin 100·1 ± 2·77 mg L(-1) ), with a positive correlation between lesional and perilesional skin zinc (r = 0·91, P < 0·01). Oral zinc supplementation significantly increased serum and skin zinc levels (by 159% and 4%, respectively; P < 0·05). CONCLUSIONS: NAE is associated with decreased serum and skin zinc levels. Oral zinc supplementation corrects decreased levels of plasma and skin zinc much earlier than the desired clinical benefits appear.

Investigation of self-organizing oscillator networks for use in clustering microarray data.

The self-organizing oscillator network (SOON) is a comparatively new clustering algorithm that does not require the knowledge of the number of clusters. The SOON is distance based, and its clustering behavior is different to density-based algorithms in a number of ways. This paper examines the effect of adjusting the control parameters of the SOON with four different datasets; the first is a (communications) modulation dataset representing one modulation scheme under a variety of noise conditions. This allows the assessment of the behavior of the algorithm with data varying between highly separable and nonseparable cases. The main thrust of this paper is to evaluate its efficacy in biological datasets. The second is taken from microarray experiments on the cell cycle of yeast, while the third and the fourth represent two microarray cancer datasets, i.e., the lymphoma and the liver cancer datasets. The paper demonstrates that the SOON is a viable tool to analyze these problems, and can add many useful insights to the biological data that may not always be available using other clustering methods.

Central effects of beta-adrenoceptor antagonists.

The central effects of atenolol, a cardioselective beta-adrenoceptor antagonist, were investigated in six healthy men. Two flash-fusion threshold (2FFT), simple reaction time (SRT), digital copying (DCT), symbol-digit modalities (SDMT), and Gibson's spiral maze tests (GSMT) and mood rating scales for tension, alertness, depression, detachment, and anxiety were used. Each subject took 50, 100, 200, and 400 mg atenolol and identical placebo orally in a randomized, double-blind, crossover study and the psychomotor tests were performed at 0, 2, 3, 5, and 8 hr. 2FFT was prolonged at 3 hr after all doses and at 2 and 5 hr with 100, 200, and 400 mg. The maximum effect was achieved with 200 mg and mean 2FFT correlated with mean plasma atenolol concentration. SRTs were prolonged after all doses at between 2 and 5 hr. The DCT and the retest gain of the SDMT were both lower than after placebo at 2 hr with 100, 200, and 400 mg. The time taken to perform the GSMT was not altered by active drug, but the number of errors was lower at 2 hr with 100 and 200 mg. The self-rating mood scales showed a subjective decrease in tension 2 hr after 400 mg. The results show that atenolol exerts central effects in man.

Induction of microsomal enzyme activity by flupenthixol in chronic schizophrenics.

The effect of long-term treatment with flupenthixol on hepatic microsomal enzyme activity was studied in 12 chronic schizophrenic outpatients who had been receiving two weekly maintenance doses for at least 6 months. Antipyrine half-life was measured in the 12 patients while they continued to receive the drug. Flupenthixol was then discontinued for 6 weeks and antipyrine half-life was repeated in 7 of the 12 patients. In the 12 patients the plasma antipyrine elimination half-life was 4-24 h (mean 9.73 +/- 1.61 h) when receiving flupenthixol and there was a significant negative correlation between antipyrine half-life and the dose of flupenthixol (r = 0.582, P less than 0.05). In the seven patients to whom antipyrine was given on two occasions, antipyrine half-life was 7.33 +/- 1.07 h and 12.04 +/- 1.87 h on and off flupenthixol treatment respectively. The clearance significantly decreased when flupenthixol was discontinued, but there was no change in the apparent volume of distribution.

Effect of Toxoplasma gondii on histopathology and histochemistry or reticuloendothelial system in experimental animals.

The effect of acute and chronic infections by Toxoplasma gondii on the spleen, thymus and liver of mice and rats, and on their antibody response has been studied. In acute infection while the splenic weight increased the thymic weight decreased. The histopathological studies demonstrated lymphocytic depletion of splenic follicles and thymic cortex. Numerous phagocytes and plasma cells were seen in the red pulp and thymic medulla. Vascular congestion and haemorrhages were marked. The liver cells showed degeneration which progressed from hydropic to fatty. The succinic dehydrogenase activity of damaged cells was decreased, while the phosphatase activity was increased. The parasites were seen in some liver cells. Marked cellular infiltration was observed around the blood vessels in the form of granulomata. The reticuloendothelial cells, Kupffer cells and phagocytes showed higher alkaline phosphatase activity. In chronic infection the thymus showed early lymphocytic depletion then returned to normal. The splenic weight was increased and the follicles were enlarged with the presence of immunoblasts in the germinal centres. The cords of the red pulp were thickened and contained numerous plasma cells. Most of the liver cells were normal with normal enzymatic activity but small foci of necrosis were seen. There was a gradual increase in antibody response in both acute and chronic infections. It was concluded from the results that acute infection mainly produced toxic effects, whereas chronic infection produced immunological responses.

Experimental concomitant toxoplasma and malaria infection in rats.

The effect of concomitant toxoplasma and malaria infection on the reticuloendothelial system was investigated in rats. This was evaluated by the level of plasmodial parasitaemia; humoral antibody response; effect on splenic weight; histopathological changes in thymus and spleen; histopathological and histochemical changes in liver. The parasitaemia appeared after 2 days in single malaria and concomitant infections. The peak was reached after 6 days with single and precedent malaria, and after 10 days with precedent toxoplasma. The clearance of parasitaemia was delayed to 30 days with concomitant infections instead of 14 days with single malaria. Higher than normal malarial antibody levels were reached with precedent toxoplasma, while the toxoplasma antibodies were lower than normal in both concomitant infections. There was a significant increase in splenic weight in both precedent malaria and toxoplasma, followed by a decrease which did not return to normal in case of precedent malaria. The thymus was packed with thymocytes in precedent malaria, while depletion in the cortex occurred in precedent toxoplasma. In the liver, there was glycogen depletion and decrease in succinic dehydrogenase activity in both concomitant infections. Choline esterase activity in precedent malaria was decreased and returned to normal on day 40 while in precedent toxoplasma the activity was normal all through the period. The alkaline phosphatase activity was decreased and returned to normal on day 40 in both concomitant infections.

Emergence of foot-and-mouth disease virus SAT 2 in Egypt during 2012.

The epidemiology of foot-and-mouth disease (FMD) in North Africa is complicated by the co-circulation of endemic FMD viruses (FMDV), as well as sporadic incursions of exotic viral strains from the Middle East and Sub-Saharan Africa. This report describes the molecular characterization of SAT 2 FMD viruses that have caused widespread field outbreaks of FMD in Egypt during February and March 2012. Phylogenetic analysis showed that viruses from these outbreaks fell into two distinct lineages within the SAT 2 topotype VII, which were distinct from a contemporary SAT 2 lineage of the same toptype from Libya. These were the first FMD outbreaks due to this serotype in Egypt since 1950 and required the development of a tailored real-time reverse-transcription PCR assay that can be used in the laboratory to distinguish FMD viruses of these lineages from other endemic FMD viruses that might be present in North Africa. These data highlight the ease by which FMDV can cross international boundaries and emphasize the importance of deploying systems to continuously monitor the global epidemiology of this disease.

Central effects of single oral doses of propranolol in man.

The central effects of propranolol, a lipophilic beta-adrenoceptor antagonist, were investigated in six healthy male volunteers using two flash fusion threshold (2FFT), simple reaction time (SRT), digital copying test (DCT), symbol digit modalities test (SDMT), Gibson spiral maze test (GSMT) and mood rating scales for tension, alertness, depression, detachment and anxiety. Compared to placebo, 2FFT was prolonged by propranolol 40, 80 and 160 mg at one or more times tested but not by propranolol 320 mg: the largest effect was seen at 3 h after 40 mg, and the effects of 40, 80 and 160 mg were significantly greater than 320 mg at 2 h. SRTs were significantly prolonged by all doses of propranolol at 2 and 3 h and by 40 and 80 mg doses at 5 h. DCT was lowered by 40 and 80 mg at 2 and 3 h by 80 mg at 5 h, and by 320 mg at 2 h, but the 160 mg dose had no effect. Propranolol impaired the expected retest gain of the SDMT with all doses except 320 mg and at 2 h after 40, 80 and 160 mg, performance was actually worsened. Mood rating scales showed increased detachment with 40 mg and decreased alertness with 80 and 320 mg. The results show that propranolol has central effects in man: the effects appeared to be greater with lower doses, 40 and 80 mg, than with higher doses, 160 and 320 mg.

Endoscopic diagnosis of gastric varices.

In this retrospective study, the presence and appearance of gastric varices were analyzed among patients presenting at Kasr El Aini Hospital with variceal bleeding during the period from 1984 to 1989. Two groups of patients were studied. The first group included 970 patients with documented variceal bleeding with no history of sclerotherapy. Of these patients 6.7%, had concomitant gastric varices, and 27.1% had direct gastric extension of esophageal varices (mostly of grade 3). Gastric varices alone, without esophageal varices, were found in five cases (0.5%). The second group was a subgroup, and included 376 patients who underwent complete sclerotherapeutic eradication of varices restricted to the esophagus and were without gastric varices at the first presentation. Eleven of these patients (2.9%) developed secondary gastric varices. There was no correlation between the risk of bleeding from primary gastric varices (seen at the first presentation) and the grade of the esophageal varices. There were more bleeding episodes from large gastric varices (35.4% for the cauliflower and 16.9% for the cystic forms) than from the small varices, i.e. ruga-like and network-like gastric varices. The study also shows that the secondary development of gastric varices after endoscopic variceal sclerotherapy is a rare event, and that there was no risk of bleeding from the secondary gastric varices. Patients with esophageal varices with gastric extension had a small risk of bleeding from their gastric varices (5.2%).

Experimental trichinosis: effect of immunosuppression on the host-parasite system.

Experimental trichinosis in immunocompetent verus immunosuppressed albino rats was studied over a period of two months. The immunosuppressed ones showed significant delay in expulsion of adult worms, significant increase in the yield of muscle larvae, lower IFA titres and delayed encystation of muscle larvae with mild cellular infiltration. Specific antigen deposits detected in the muscles and different tissues of the immunosuppressed rats indicated augmentation of circulating antigens. In both groups, the liver, kidney, lung, brain and testes showed nonspecific pathological changes but larvae were never detected in examined sections. Incidentally, on the 14th post-infection day, two immunocompetent rats were found pregnant, and near-full-term embryos showed more deposition of Trichinella antigens in most of their tissues indicating placental passage of circulating antigens. This study indicates that in patients receiving immunosuppressive drugs, possible exposure to T. spiralis infection will result in severe manifestations or complications.

New Guaianolides and Farnesol Derivatives from Arctotis arctotoides1.

The aerial parts of ARCTOTIS ARCTOTOIDES afforded eight known sesquiterpene lactones and three new ones, the 11beta,13-dihydroguaianolides 9 and 10 as well as the chlorohydrine 8. Furthermore two 2Z-farnesol derivatives 12 and 13 were isolated. The structures were elucidated by highfield (1)H-NMR. The stereochemistry of several compounds has been revised.