Diarrheal illness among infants and toddlers in day care centers: effects of active surveillance and staff training without subsequent monitoring

From October 1981 to September 1984, the authors conducted a three-year longitudinal study of diarrhea among infants and toddlers attending day care centers in Maricopa County, Arizona. In the third year of study, they evaluated the effects on diarrhea rates of staff training without external monitoring and of active surveillance conducted throughout the study. From 21 study day care centers, they randomly selected 10 ("intervention day care centers") to receive staff training in procedures to reduce transmission of infectious diarrhea. Continuing active surveillance in the 10 intervention and 11 control day care centers found no difference between diarrhea rates in intervention day care centers in the pre- and posttraining years and no difference between diarrhea rates in the two groups of centers either before or after the training intervention. Biweekly family-based surveys during the two months after training also demonstrated no difference between infant-toddler diarrhea rates in intervention and control day care centers. These surveys found the 21 study day care centers to have significantly higher diarrhea rates than did day care homes or households not using day care, but significantly lower rates than day care centers not included in the active surveillance. Continuous surveillance without training was associated with a significant decrease in diarrheal illness during the course of longitudinal study. One-time staff training without subsequent monitoring did not result in additional decreases and did not lower day care center diarrhea rates to the levels observed in day care homes and households not using day care.     

Clinical comparative study of optimized metronidazole loaded lipid nanocarrier vaginal emulgel for management of bacterial vaginosis and its recurrence

The main focus of the current work was to design, evaluate and clinically compare the efficiency of novel metronidazole (MTD) loaded solid lipid nanoparticles (SLNs) vaginal emulgel with the marketed vaginal gel (Metron^®) against Bacterial vaginosis (BV). Eight formulations were fabricated using 2³ full factorial design and prepared by stearic acid and tween 80 as solid lipid and surfactant, respectively. Lipid and surfactant concentrations in addition to sonication amplitude were chosen as the independent variables (X₁–X₃). Then, the prepared MTD loaded SLNs were evaluated based on the dependent variables which were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative % drug release for 24 h (Y₁–Y₅). The in vitro release study exhibited a sustained release of MTD from the SLNs up to 24 h. The optimal MTD loaded SLNs showed nanosized particles (256 nm) with EE% (52%), and an acceptable ZP value (−29.5 mV). Also, the optimized MTD-SLNs formulation was incorporated into Carbopol emulgel and investigated clinically for its effect against BV. Clinical studies recorded significant enhancement in therapeutic response of MTD from optimized SLNs vaginal emulgel formulation regarding the clinical treatment (p < .05) and low recurrence rate (p < .001) against the marketed product. In conclusion, our findings recommend that the fabricated MTD loaded SLNs vaginal emulgel have significant therapeutic effect in terms of BV management over commercially obtainable marketed vaginal gel (Metron^®).     

Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms

Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa‐B (NF‐кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), intracellular adhesion molecule (ICAM‐1), monocellular chemoattractant protein‐1 (MCP‐1), tumour growth factor‐ β (TGF‐β), caspase‐3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator‐activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.     

Modulation of Multidrug Resistance by SDZ PSC 833 in Leukemic and Solid-tumor-bearing Mouse Models

P-Glycoprotein inhibitors, including the nonimmunosuppressive cyclosporin D analog SDZ PSC 833 (PSC 833), have been developed to circumvent multidrug resistance. In the present study, the potential of PSC 833 in reversing multidrug resistance was evaluated in various systemic treatment models with leukemic and solid-tumor-bearing mice. Having a relatively wide therapeutic window of daily p.o. doses from 12.5 to 75 mg/kg, PSC 833 significantly improved the antileukemic activity of the anticancer drugs adriamycin (ADM), vincristine (VCR) and etoposide (VP-16) given i.p. or i.v. against i.p.-inoculated vincristine-resistant P388 tumor (P388/VCR). PSC 833 in combination with i.p.-injected anticancer drugs in optimal schedule and dosage induced apparent cures in some leukemic mice, whereas no cures were obtained with the cyclosporin A/anticancer drug combinations. PSC 833 combined with i.v.-injected anticancer drugs was highly active, but not curative, against P388/VCR and parental P388 tumors (maximum T/C>175%). PSC 833 in combination with intravenous treatment with ADM showed prominent anti-solid-tumor activity against s.c.-inoculated colon adenocarcinoma 26 and human colorectal adenocarcinoma HCT-15. Against colon adenocarcinoma 26, the PSC 833/ADM combinations induced cure in two or three of six mice. PSC 833/ADM combinations significantly inhibited the growth of the tumor with maximum percent inhibitions of 83 and 73% in the early and advanced stages of the HCT-15 tumor models, respectively. The present study demonstrated that PSC 833 is highly active in potentiating the antitumor activity of systemically administered ADM, VCR and VP-16 against four murine and human tumors with a relatively wide therapeutic window of daily p.o. dose range of 12.5–100 mg/kg.     

Mechanisms whereby cytotoxic T lymphocytes damage guinea-pig ventricular myocytes in vitro

We studied possible mechanisms whereby cytotoxic T lymphocytes (CTL) damage the myocardium during the immunological rejection of the transplanted heart, by investigating the in vitro interaction between CTL and cardiac myocytes. We utilized the patch-clamp technique to record membrane currents and action potentials from concanavalin A-treated guinea-pig ventricular myocytes conjugated to mouse peritoneal exudate CTL (PEL). PEL-myocyte interaction reduced action potential duration at 50% repolarization (APD₅₀) from 731.7±57.8 to 195.3±58.0 ms, action potential amplitude from 134.9±1.9 to 104.2±6.2 mV and resting membrane potential (V_m) from –80.9±0.5 to –72.5±1.5 mV. These changes were accompanied by generation of delayed afterdepolarizations, indicative of intracellular [Ca²⁺] overload. The electrophysiological alterations were associated with myocyte shortening (within 28.9±2.8 min) followed by complete cell destruction (within 43.5±4.3 min). To determine whether intracellular Ca²⁺ stores were involved in PEL-induced myocyte damage, the protective effects of ryanodine and caffeine were investigated. While ryanodine (10 M) delayed the electrophysiological and morphological alterations, caffeine (5 mM) provided significant protection, suggesting that Ca²⁺ release from intracellular stores contributes to PEL-induced damage to the myocytes. Based on our findings, we suggest that the functional derangements seen in myocyte-lymphocyte conjugates can contribute to the overall decline in cardiac function during heart transplant rejection.     

Anaplasma phagocytophilum utilizes multiple host evasion mechanisms to thwart NADPH oxidase-mediated killing during neutrophil infection

Anaplasma phagocytophilum, the etiologic agent of human anaplasmosis, is a bacterial pathogen that specifically colonizes neutrophils. Neutrophils utilize the NADPH oxidase complex to generate superoxide (O(2)(-)) and initiate oxidative killing of microorganisms. A. phagocytophilum's unique tropism for neutrophils, however, indicates that it subverts and/or avoids oxidative killing. We therefore examined the effects of A. phagocytophilum infection on neutrophil NADPH oxidase assembly and reactive oxygen species (ROS) production. Following neutrophil binding, Anaplasma invasion requires at least 240 min. During its prolonged association with the neutrophil plasma membrane, A. phagocytophilum stimulates NADPH oxidase assembly, as indicated by increased cytochrome b(558) mobilization to the membrane, as well as colocalization of Rac and p22(phox). This initial stimulation taxes the host neutrophil's finite oxidase reserves, as demonstrated by time- and bacterial-dose-dependent decreases in secondary activation by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA). This stimulation is modest, however, and does not diminish oxidase stores to nearly the extent that Escherichia coli, serum-opsonized zymosan, FMLP, or PMA do. Despite the apparent activation of NADPH oxidase, no change in ROS-dependent chemiluminescence is observed upon the addition of A. phagocytophilum to neutrophils, indicating that the bacterium may scavenge exogenous O(2)(-). Indeed, A. phagocytophilum rapidly detoxifies O(2)(-) in a cell-free system. Once internalized, the bacterium resides within a protective vacuole that excludes p22(phox) and gp91(phox). Thus, A. phagocytophilum employs at least two strategies to protect itself from neutrophil NADPH oxidase-mediated killing.     

Patterns of Primary Immunodeficiency Disorders Among a Highly Consanguineous Population: Cairo University Pediatric Hospital’s 5-Year Experience

Introduction

Primary immunodeficiency disorders (PIDs) are heterogeneous disorders that mainly present with severe, persistent, unusual, or recurrent infections in childhood. Reports from different parts of the world indicate a difference between Western and Eastern populations.

Aim

The aim of this study was to report on the different patterns of PIDs and identify subgroup characteristics in a highly consanguineous population in Egypt.

Methods

We performed a retrospective chart review for children below 18 years diagnosed with PID at Cairo University Pediatric Hospital from 2010 to 2014.

Results

Four hundred seventy-six children were diagnosed with PID disorders. Major categories included combined immunodeficiency disorders, which constituted a large proportion (30 %) of cases, along with predominantly antibody disorders (18 %) followed by syndromic combined disorders (16.8 %), phagocytic disorders (13.2 %), immune dysregulation disorders (10.5 %), and autoinflammatory disorders (9 %).

Conclusion

PIDs have different patterns within inbred populations with high consanguinity.

     

Effects of age,period, and cohort on stroke mortality among the Lithuanian urban population during the 24-year follow-up period

The main purpose of this paper was to assess the effects of age, period, and cohort on stroke mortality among the urban Lithuanian population. Routine stroke mortality data among the Lithuanian urban population aged 25–64 years (1041 men and 724 women) between 1980 and 2004 were obtained from the official Kaunas region mortality register and classified by codes 430–438 and 160–169 in the 9^th and 10^th revisions of the International Classifications of Diseases (ICD), respectively. Mortality rates per 100,000 persons for men and women were age-adjusted using the age distribution of the European Standard Population. Goodness of fit of the Poisson regression models was evaluated using the Pearson and Freeman-Tukey residuals. During the study period, mortality rates decreased from 46.8 to 33.0 per 100,000 for men, and from 20.2 to 18.1 per 100,000 for women (average annual decrease of −1.3%, p<0.1 for men, and −1.6%, p<0.03 for women). An age effect was present in both sexes. The definite upward period effect was observed from 1990 to 1994 both among men and women, and was followed by a sharp fall during 2000–2004. Cohort and period effects have contained relevant information that partially explained trends in stroke mortality among 25–64 year-olds in the Lithuanian urban population. The Poisson regression models could be applied for the examination and explanation of the different causes of the population mortality.