Nuha Nuwayri-Salti

Recurrent molar pregnancies in a family with extensive intermarriage: Report of a family and review of the literature

Background Familial recurrent molar pregnancies are exceedingly rare. The genetic basis for recurrent moles is not well understood, and its association with major human lymphocytic antigen histocompatibility is debatable. The purpose of this report is to present a family with extensive intermarriage and recurrent molar pregnancies with some emphasis on the result of the human lymphocytic antigentyping. Case Two sisters, both married to first-degree cousins, had three and five pathologically confirmed molar pregnancies, respectively. A second-degree cousin, also married to her first-degree cousin, is also reported to have had five consecutive moles. Chromosomal analysis and human lymphocytic antigen-typing on the two sisters and their spouses was performed. Human lymphocytic antigen-typing was compared to a cross-sectional sample of our population. This showed a high incidence of unusual human lymphocytic antigens in these family members. Conclusion In families with extensive intermarriage and recurrent molar pregnancies, patients and their spouses may have unusual human lymphocytic antigen histocompatibility, which supports the possibility of a strong genetic predisposition expressed at the level of major histocompatibility class I and li gene translation.

Effect of insulin and angiotensin II receptor subtype-1 antagonist on myocardial remodelling in rats with insulin-dependent diabetes mellitus

Objectives To assess the role of insulin or an angiotensin II receptor antagonist (losartan), or both, in preventing cardiomyocyte damage in rats suffering from insulin-dependent diabetes mellitus (IDDM), and to correlate it with insulin receptor modulation at the cardiomyocyte, coronary endothelium and skeletal muscle cell level. Design Animals were divided into groups of normal rats, diabetic rats, and diabetic rats given insulin, each subdivided into a control group and an experimental group treated with losartan. Methods The animals were killed 1 month after enrollment to the study. Perfusion of the heart with iodine-125-labelled insulin was carried out for all the groups and the binding kinetics of insulin to its receptors on the coronary endothelial cells and the cardiomyocytes were determined using a physical/mathematical model. In addition, tissue samples from the heart and intercostal skeletal muscle were snap frozen and used for histological, indirect immunofluorescence and western blot analysis. Results Cardiac muscle from diabetic animals exhibited diffuse cardiomyopathic changes consisting of widespread vacuolation, loss of striation and cellular hypertrophy, which were reduced and even prevented by treatment with insulin and losartan. In addition, losartan seemed to mediate the upregulation of insulin receptor density on cardiomyocytes and skeletal muscle, and increase insulin receptor affinity at the coronary endothelial site. Finally, treatment with losartan induced a significant decrease in glucose concentrations in the diabetic group compared with the appropriate controls. Conclusions Addition of losartan to the standard insulin treatment in non-hypertensive animals with IDDM offers new benefits concerning cardiac protection and prevention of damage. This may be attributed, in part, to insulin receptor density and sensitization.

Direct non-insect-vector transmission of Leishmania parasites in mice.

Abstract Animal to animal non-vector transmission of Leishmania major was investigated in Balb/c mice, a strain known for its susceptibility to this parasite. Both overt or inapparent infection (documented by positive spleen cultures) was possible after prolonged contact with infected animals. Similarly transmission of infection from infected mothers to their offspring was documented.

Immunologic and Anti-Immunosuppressive Effects of Vitamin A

The effects of vitamin A alcohol on cell-mediated immunity in vitro and its ability to prevent the immunosuppressive effects of prednisolone and cyclophosphamide in vivo were studied in mice. Lymphocytes from Calmette-Guérin bacillus (BCG) sensitized mice were stimulated specifically with purified protein derivative (PPD) and nonspecifically with phytohemagglutinin (PHA). In the vitamin A injected animals there was significant enhancement of the spleen lymphocyte transformation not only in the PPD-sensitive cells but also in the T cells at large. In addition, vitamin A was able to restore to normal the cellular and humoral forms of immunity in prednisolone and cyclophosphamide-treated animals. It is suggested that vitamin A in nontoxic doses may have a role in enhancing the responses to weak immunogens and in reversing immunosuppression.

Role of glucagon-like peptide-1 and its agonists on early prevention of cardiac remodeling in type 1 diabetic rat hearts.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from intestinal L cells upon nutrients ingestion, and is currently used for treating diabetes mellitus. It plays an important role in receptor modulation and cross talk with insulin at the coronary endothelium (CE) and cardiomyocytes (CM) in diabetic type 1 rat heart model. We studied the effects of insulin, GLP-1 analogues (exendin-4), and dipeptidyl peptidase-IV (DPP-IV) inhibitor on GLP-1 cardiac receptor modulation. The binding affinity of GLP-1 to its receptor on CE and CM was calculated using a rat heart perfusion model with [(125)I]-GLP-1(7-36). Tissue samples from the heart were used for immunostaining and Western blot analyses. GLP-1 systemic blood levels were measured using ELISA. GLP-1 binding affinity (τ) increased on the CE (0.33 ± 0.01 vs. 0.25 ± 0.01 min; p < 0.001) and decreased on the CM (0.29 ± 0.02 vs. 0.43 ± 0.02 min; p < 0.001) in the diabetic non-treated rats when compared to normal. There was normalization of τ back to baseline on the CE and CM levels with insulin and DPP-IV inhibitor treatment, respectively. Histological sections and immunofluorescence showed receptor up-regulation in diabetic rats with significant decrease and even normalization with the different treatment strategies. Systemic GLP-1 levels increased after 14 days of diabetes induction (10 ± 3.7 vs. 103 ± 58 pM; p = 0.0005). In conclusion, there is a significant GLP-1 receptor affinity modulation on the CE and CM levels in rats with diabetes type 1, and a cross talk with GLP-1 analogues in early prevention of cardiac remodeling.

Detection of Leishmania parasites in the blood of patients with isolated cutaneous leishmaniasis

BACKGROUND The consequences of the spread of Leishmania parasites to the blood from lesions in patients with cutaneous leishmaniasis are numerous. To assess the magnitude of this invasion we conducted the present study on patients referred to the American University of Beirut Medical Center for cutaneous leishmaniasis. METHODS Patients referred for the management of cutaneous leishmaniasis were included in the study. Skin and blood cultures for Leishmania were taken from these patients. RESULTS One hundred sixty-two patients were proven to have cutaneous leishmaniasis by pathology; 52% were males and 44% females (gender information was missing for 4%). Patient age ranged from 5 months to 70 years. None of the patients had received treatment for Leishmania. We obtained parasite isolates from 85 patients (52.5%), proven by cultures from skin and blood/blood components. Interestingly, the parasite was isolated in the blood and blood components of 50 patients (30.9%). Isoenzyme analysis confirmed the fact that the organisms in blood and skin were the same; from the 28 isolates that were positive in both skin and blood, eight isolates were Leishmania major and two were Leishmania tropica. The remaining isolates, whether positive in both blood and skin or in either of these tissues, skin or blood and its products, were Leishmania infantum sensu lato. CONCLUSIONS In the current study, the detection rate of parasites in the blood of patients with cutaneous leishmaniasis was high. This illustrates the invasive characteristic of the parasite that has escaped the skin. Testing should be considered in areas other than Lebanon, especially around the Mediterranean basin. Whether these findings support the administration of systemic treatment for cutaneous leishmaniasis or not needs to be confirmed in larger prospective studies.

Identification of Lebanese dermotropic putative Leishmania archibaldi isolates by gp63 PCR-RFLP.

Leishmania stocks isolated from cutaneous lesions in Lebanon were characterized by PCR methods. The stocks were typed as putative L. (L.) archibaldi (gp63 PCR-RFLP), belonging to 2 different genotypes (PCR-based schizodeme analysis). This constitutes the first report on the presence of L. (L.) archibaldi in the Middle East.

Effect of systemic insulin and angiotensin II receptor subtype-1 antagonist on endothelin-1 receptor subtype(s) regulation and binding in diabetic rat heart.

This study reports on the regulation and remodeling role of endothelin-1 (ET-1) and its receptor subtypes, ET(A)-Rs/ET(B)-Rs, at the coronary endothelium (CE) and cardiomyocyte (CM) sites. It is carried out in normal and normotensive rats with streptozotocin-induced diabetes mellitus receiving different treatment modalities. Normal rats were divided into two groups, namely a placebo (N) and a losartan-treated (NL), and diabetic rats into four groups receiving placebo (D), insulin-treated (DI), losartan-treated (DL), and insulin/losartan-treated (DIL) respectively. Binding kinetics of ET-1 to ET(A)-Rs/ET(B)-Rs on CE and CMs were assessed in the above groups to try to explain the effect of therapeutic doses of an angiotensin II receptor subtype-1 blocker on the dynamics of this ligand and its receptor in insulin supplemented diabetic animals. Each group was divided into two subgroups: CHAPS-untreated and CHAPS-treated rat hearts perfused with [125I]ET-1 to respectively estimate ET-1 binding affinity (tau = 1/k-n) to its receptor subtype(s) on CE and CMs using mathematical modeling describing a 1:1 reversible binding stoichiometry. Heart perfusion results revealed that insulin treatment significantly decreased tau on CE but not on CMs in diabetic rats. In diabetics treated with losartan, an increase in tau value on CE but not on CMs was noted. Cotreatment of diabetic rats with insulin and losartan normalized tau on CE but decreased it on CMs. Western blot, using snap-frozen heart tissues, revealed increase in ET(A)-R density in all diabetic groups. However, significant decrease in ET(B)-R density was observed in all groups compared to the normal, and was reconfirmed by immunohistochemical analysis. In conclusion, coadministration of insulin and losartan in nonhypertensive animals suffering from diabetes type 1 may offer new cardiac protection benefits by improving coronary blood flow and cardiomyocyte contractility through modulating ET-1 receptor subtypes density and affinity at CE and CM sites.

The epidemiology of leishmaniases in Lebanon.

The prevalence of leishmaniasis in Lebanon was studied in 1993-97 for a Lebanese population sample of about 81,000 subjects (60% rural and 40% urban) constituting roughly 3.4% of the total population. The prevalence of cutaneous leishmaniasis was found to be 0.18% in the rural versus 0.41% in the urban areas. Visceral leishmaniasis was practically non-existent in both environments. In addition, skin tests were done and anti-Leishmania antibodies were sought in a sample of the population at risk in the rural area. Skin tests were positive in 2.5% of the tested subjects, and 1% of the normal population had elevated levels of anti-Leishmania antibodies. The difference between the prevalence of clinical disease and positive skin testing and/or antibodies may be due to the existence of past or present subclinical disease. An unexpected finding was that the prevalent dermotropic parasite in Lebanon belongs to the L. donovani complex. Further characterization of the isolates by molecular techniques and definition of the transmission cycle of this parasite may explain our epidemiological findings.

Effects of rosiglitazone (PPAR γ agonist) on the myocardium in non‐hypertensive diabetic rats 罗格列酮（PPAR γ 激动剂）对非高血压糖尿病大鼠的心肌的影响

There is ongoing controversy regarding the safety of rosiglitazone and its effects on the myocardium, in some cases causing severe cardiac pathology and even in some instances mortality. In this study we aimed at examining the effects of pharmacologic doses of rosiglitazone on cardiomyocytes in diabetic non‐cardiac rats receiving sub‐optimal doses of insulin.