Facial amphiphilicity index correlating chemical structures with antimicrobial efficacy.

Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers. Vast efforts have been dedicated to small molecular, macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation, including local facial amphiphilicity and global amphiphilicity. This work conceptualizes Facial Amphiphilicity Index (FAI) as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy. FAI is a ratio of numbers of charges to rings, representing both compositions of hydrophilicity and hydrophobicity. Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria. Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs. Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid. While low and high FAIs respectively lead to higher and lower antimicrobial efficacy, in consideration of cytotoxicity, the sweet spot is typically suited with intermediate FAIs for each specific system. This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes. The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.

Malaria Transmission and Spillover across the Peru-Ecuador Border: A Spatiotemporal Analysis.

Border regions have been implicated as important hot spots of malaria transmission, particularly in Latin America, where free movement rights mean that residents can cross borders using just a national ID. Additionally, rural livelihoods largely depend on short-term migrants traveling across borders via the Amazon's river networks to work in extractive industries, such as logging. As a result, there is likely considerable spillover across country borders, particularly along the border between Peru and Ecuador. This border region exhibits a steep gradient of transmission intensity, with Peru having a much higher incidence of malaria than Ecuador. In this paper, we integrate 13 years of weekly malaria surveillance data collected at the district level in Peru and the canton level in Ecuador, and leverage hierarchical Bayesian spatiotemporal regression models to identify the degree to which malaria transmission in Ecuador is influenced by transmission in Peru. We find that increased case incidence in Peruvian districts that border the Ecuadorian Amazon is associated with increased incidence in Ecuador. Our results highlight the importance of coordinated malaria control across borders.

Surgical importance of arterial segments of human kidneys: an angiography and corrosion cast study.

OBJECTIVE: Variations in the arterial supply of human kidney have been observed frequently, either in routine dissections or surgical practice. The main objective of the present study was to describe the arterial segmental pattern of human kidneys and its variation by angiography and corrosion cast techniques. MATERIALS AND METHODS: Forty kidneys were washed and a plastic cannula was inserted into renal artery and the omnipaque dye was injected into it and X-ray was taken. The corrosion casts were prepared by injecting coloured acetate butyrate (CAB) granules solution. RESULTS: Five vascular segments of kidney were seen based on the branching pattern of the renal artery by angiography and corrosion cast techniques. The renal artery was divided into anterior and posterior branches. The anterior branch further divided into four branches viz. apical segmental artery (ASA), Upper segmental artery (USA), middle segmental artery (MSA), lower segmental artery (LSA) while the posterior branch continue as posterior segmental artery. The origins of segmental arteries were variable. In 60% cases apical segmental artery (ASA) had common origin with upper segmental artery (USA) while in 40% cases it took origin directly from the main renal artery. Similarly the variations in the origin of the other branches of anterior division of renal artery were observed. The posterior segmental artery (PSA) however was single and comparatively small and supplied the posterior surface of the kidney. CONCLUSION: The knowledge of the vascular pattern of the kidney is thus important for the purpose of angiography and surgical procedures especially for nephrectomy and kidney transplantation.

A comparative study of apoptosis in placentas of normal and preeclamptic Indian pregnant women by TUNEL assay and M30 immunostaining.

BACKGROUND: Preeclampsia is a unique life-threatening disorder of human pregnancy associated with the abnormal placentation caused by the inadequate trophoblastic invasion due to altered apoptosis of these cells. The aim of the present study was to assess and compare the apoptosis in trophoblastic cells in various zones (villous and extravillous) of placentas of preeclamptic and normotensive nonproteinuric pregnant women. METHODS: Hematoxylin eosin staining, TUNEL assay and M30 immunostaining techniques were used for studying apoptosis in trophoblastic cells of placentas of two groups. The results of apoptotic indices by these techniques were compared in preeclamptic group. RESULTS: The TUNEL apoptotic indices were higher in all the zones of placentas of preeclamptic group as compared to control group though the results were not statistically significant. M30 immunostaining also gave higher apoptotic indices in all the zones of preeclamptic placentas as compared to the normal group but the result of apoptotic index of basal plate was not statistically significant. M30 immunostaining was absent in stromal cells. CONCLUSION: In our study, the trophoblastic apoptotic rates were more in villous as well as extravillous zones of preeclamptic placentas as compared to normal placentas and M30 immunostaining was found to be more sensitive and specific for the apoptotic trophoblastic cells as compared to TUNEL assay.

Role of oxidative stress markers and antioxidants in the placenta of preeclamptic patients.

AIM: The present study aimed to evaluate and compare the placental variables of oxidative stress markers in preeclamptic women. METHODS: A total of 60 placentas were collected. Of these, 30 were obtained from normotensive pregnancies, and 30 from pregnancies with preeclampsia as per International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Each placental tissue was analyzed for levels of pro-oxidant (malondialdehyde) and antioxidants (glutathione and superoxide dismutase) using the standard enzymatic assays. RESULTS: Malondialdehyde levels were significantly higher (12.21 ± 4.1 versus 4.7 ± 2.1 nmol/g tissue, P < 0.0001) and glutathione (GSH) levels were significantly lower (0.46 ± 0.37 versus 1.03 ± 0.43 µmol/g tissue, P < 0.0001) in the placentas of preeclamptic women when compared to those of normal pregnancies. Though not statistically significant, decreases in superoxide dismutase levels were observed in placentas of preeclamptic women (4.14 ± 2.25 versus 5.22 ± 2.0 units/mg tissue protein, P < 0.055). Receiver operator characteristic curve analysis of malondialdehyde revealed a sensitivity of 87% and specificity of 87%, at a cutoff value 6.5 nmol/g. Similarly, GSH had a sensitivity of 77% and a specificity of 77% at a cutoff value 0.62 µmol/g. CONCLUSION: The present study demonstrated that increased placental lipid peroxidation and decreased levels of antioxidants may play an important role in the pathogenesis of preeclampsia. These findings are suggestive of involvement of oxidative stress markers in preeclamptic patients.

Circulating angiogenic factors in pregnancies complicated by pre-eclampsia.

BACKGROUND: Pre-eclampsia is an inflammatory disorder characterized by diffuse endothelial dysfunction possibly secondary to impaired trophoblast invasion of the spiral arteries during implantation. It is associated with alterations in maternal serum concentrations of vascular endothelial growth factor (VEGF), placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). We did a case-control study to ascertain whether pre-eclampsia is associated with changes in serum concentrations of VEGF, PIGF and sFlt-1 in Indian patients. METHODS: Serum samples were obtained from 40 women with pre-eclampsia and 40 normotensive, non-proteinuric pregnant women. The levels of VEGF, PIGF and sFlt-1 were analysed using ELISA. RESULTS: In the sera of pregnant women with pre-eclampsia, the levels of sFlt-1 were significantly higher than those in the sera of normotensive, non-proteinuric pregnantwomen (median 11295.25 v. 2936.2 pg/ml, p < 0.0001), whereas there was a significant reduction in the levels of free VEGF (mean [SD] 170.53 [36.56] pg/ml v. 254.61 [47.39] pg/ml, p < 0.0001) and PIGF (mean [SD] 236.77 [93.70] pg/ml v. 744.98 [168.55] pg/ml, p < 0.0001). CONCLUSION: An increase in sFlt-1 levels and a simultaneous decrease in free VEGF and PIGF levels in the sera of women with pre-eclampsia as compared with normotensive, nonproteinuric pregnant women suggest that an imbalance between the levels of these pro- and anti-angiogenic factors'may have a role to play in the pathogenesis of pre-eclampsia.

Mast cells in histoid lepromatous lesions

Ten patients with histoid lesions among the lepromatous leprosy cases, of both sexes in the age group of 35-65 years, were included in this study. Skin biopsy from the nodule with surrounding healthy skin of histoid lesion was taken. The biopsies were fixed in Susa solution and processed for light microscopy, 5-7u thick sections were cut and stained with hematoxylin and eosin, Toludine blue and Fite Faraco. Observations were made on the dermis to locate the mast cells and bacilli. Proliferation of mast cells and their degranulation were seen in the: histoid nodule as comparede to surrounding normal healt skin where the cells were mainly infact. The study further investigates the role of mast cells in the histopathogenesis of the disease.