BackgroundAngiogenesis was suggested to have a significant role in the pathogenesis of leprosy. However, the benefit of inhibiting angiogenesis in lepromatous leprosy patients has not previously been studied. The purpose of this study was to evaluate angiogenesis in leprosy patients before and after treatment with multidrug therapy (MDT) with and without minocycline.MethodsA total of 40 patients with lepromatous leprosy were enrolled in this study. They were categorized into two equal groups (A and B), each formed of 20 patients. Group A received World Health Organization MDT, and Group B received MDT combined with minocycline, which has a known antiangiogenic effect. Microvascular density (MVD) in dermal granuloma was evaluated in both groups by immunostaining with CD31 and CD34 markers before and after 6 months of treatment.ResultsWith CD31 immunostaining, the mean MVD in Group A significantly decreased from 39.1 ± 3.1 vessels (v)/high power field (HPF) to 16.5 ± 2.7 v/HPF, and in Group B it significantly decreased from 38.3 ± 2.5 v/HPF to 7.6 ± 1.9 v/HPF. CD34 immunostaining also showed a significant decrease of MVD from 42.2 ± 3.1 v/HPF to 18.8 ± 2.4 v/HPF in Group A, and in Group B it significantly decreased from 43.7 ± 2.3 v/HPF to 11.5 ± 1.6 v/HPF. The reduction of MVD was significantly higher in Group B compared with in Group A (P < 0.0001). Moreover, there was a significant reduction in bacterial density (assessed by bacterial index) in the cutaneous lesions of in Group B (decreased from 4.9 ± 0.3 to 1.4 ± 0.2) compared with in Group A (decreased from 5.1 ± 0.4 to 2.3 ± 0.4).ConclusionThe synergistic effect of MDT and minocycline seems to be promising in the treatment of lepromatous leprosy. It significantly reduces angiogenesis and rapidly eliminates lepra bacilli from the skin that enables a rapid control and elimination of the disease.

Neutrophils and monocytes provide a first line of defense against infections as part of the innate immune system. Here we report the integrated analysis of transcriptomic and epigenetic landscapes for circulating monocytes and neutrophils with the aim to enable downstream interpretation and functional validation of key regulatory elements in health and disease. We collected RNA-seq data, ChIP-seq of six histone modifications and of DNA methylation by bisulfite sequencing at base pair resolution from up to 6 individuals per cell type. Chromatin segmentation analyses suggested that monocytes have a higher number of cell-specific enhancer regions (4-fold) compared to neutrophils. This highly plastic epigenome is likely indicative of the greater differentiation potential of monocytes into macrophages, dendritic cells and osteoclasts. In contrast, most of the neutrophil-specific features tend to be characterized by repressed chromatin, reflective of their status as terminally differentiated cells. Enhancers were the regions where most of differences in DNA methylation between cells were observed, with monocyte-specific enhancers being generally hypomethylated. Monocytes show a substantially higher gene expression levels than neutrophils, in line with epigenomic analysis revealing that gene more active elements in monocytes. Our analyses suggest that the overexpression of c-Myc in monocytes and its binding to monocyte-specific enhancers could be an important contributor to these differences. Altogether, our study provides a comprehensive epigenetic chart of chromatin states in primary human neutrophils and monocytes, thus providing a valuable resource for studying the regulation of the human innate immune system.

In a pre-transition situation both fertility and mortality are high. However, in the process of demographic transition, fertility decline follows mortality decline and when the demographic transition is complete both these variables vary closely at a low level. In other words, both these variables behave in a way which are oomplimentaJy to each other and hence it may be hypothesised that the factors which explain variation in fertility should explain variation in mortality or vice versa. Nevertheless, the strength and sometimes even direction of these determinants may vary from time to time and from place to place. Presently, Pakistan is in the process of demographic transition. By using the 1990-91 Pakistan Demographic and Health Survey data, here in this exercise, an attempt is made to identify and investigate' the similarities and the differences if any, in the determinants of both fertility and mortality.

Objective : To compare three-dimensional transvaginal sonography (3D-TYS) (non invasive) and hysteroscopy (minimally invasive) as a diagnostic tool in patients suffering from abnormal uterine bleeding (AUB). Design: A prospective randomized comparative study. Results: Both hysteroscopy and 3D-TYS showed 100% sensitivity and specificity in diagnosing atrophic endometrium and suspecting malignancy. However, in cases of hyperplasia, 3D-TVS had the same 100% sensitivity hut less specificity than hysteroscopy. On the other hand, in cases of polyps 3D-TYS had less sensitivity and specificity than hysteroscopy. Conclusion: Both hysteroscopy (minimally invsasive) and 30-TYS have the same accuracy in diagnosing atrophic endometrium and suspected malignancy, but Hysterescopy is superior than 3D-TYS in diagnosing hyperplasia and polyps in patients suffering from AUB.Abnormal uterine bleeding is an alarming symptom that requires accurate diagnosis in order to exclude cervical and endometrial diseases.