Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.     

Preemptive Plasmapheresis and Recurrence of FSGS in High-Risk Renal Transplant Recipients

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre-transplant PP in decreasing the incidence of recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri-operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow-up (238-1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end-stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients. Definitive conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.     

Estradiol effects on the growth hormone/insulin-like growth factor-1 axis in amenorrheic athletes.

Disruption of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis has been reported and studied in menopause, hypothalamic amenorrhea, and anorexia nervosa, but not in weight-stable amenorrheic athletes. We investigated the effects of short-term transdermal estradiol on basal and exercise-stimulated serum GH, IGF-1, and associated binding proteins (IGFBP-1 and IGFBP-3) in seven weight-stable female amenorrheic athletes with percentage body fats greater that 12%. Each subject received a 72 h placebo patch followed by 144 h of transdermal estradiol. Serum samples for GH, IGF-1, IGFBP-1, and IGFBP-3 were obtained at baseline (t1), 72 hr (t2), 144 hr (t3), and during three 90-minute trials of aerobic exercise. Basal, and exercise GH, IGF-1, and IGFBP-1 were not different between trials. Baseline IGFBP-3 decreased from t1 to t2 (p = 0.04) and serum free fatty acids increased from t1 to t2, and t1 to t3 (p = 0.04, and 0.02 respectively). These findings differ from postmenopausal women, and women having weightloss-associated amenorrhea, suggesting that estrogen, exercise, and nutritional deficiencies may have independent effects on the GH/IGF-1 axis.     

Effect of gentamicin on isolated glomeruli and proximal tubules of the rabbit

Alterations in both glomerular filtration rate and tubular transport occur in clinical gentamicin nephrotoxicity. We have studied the function of isolated tubules and glomeruli from rabbits treated with gentamicin. Gentamicin was administered subcutaneously to sexually immature (1400 to 1800 gm) or sexually mature (3800 to 4600 gm) New Zealand White rabbits in a dose of 15 mg/kg twice a day. Immature rabbits were treated for 28 to 31 days and developed only minimal renal insufficiency. About one-half of the mature rabbits developed azotemia. The mature rabbits that did not become azotemic were sacrificed after 28 to 30 days, and those that became azotemic were killed when their serum creatinine reached 2.5 mg/dl or higher (10 to 24 days). Animals were anesthetized and kidneys were removed for histologic examination and isolation of tubules and glomeruli. The ratio of p-aminohippuric acid (PAH) concentration in isolated tubule cells to that in medium after incubation in 3H-PAH (1 microM) at 37 degrees C for 30 minutes (T/M PAH) was used as an indicator of transport capacity of tubules. T/M PAH ratios averaged 196 +/- 18 and 111 +/- 21 for control immature and mature rabbits, respectively, and 135 +/- 22, 80 +/- 16, and 9 +/- 2 for gentamicin-treated immature and mature nonazotemic and mature azotemic rabbits, respectively. Glomeruli were isolated and filtration induced in vitro by a transcapillary oncotic gradient. Ultrafiltration coefficient, Kf, of glomeruli of immature and mature control rabbits averaged 3.78 +/- 0.29 and 5.84 +/- 0.51 nl/minute X mm Hg. Kf from gentamicin-treated immature rabbits averaged 2.82 +/- 0.20 and from mature azotemic rabbits 3.14 +/- 0.44 nl/minute X mm Hg. Kf of both mature and immature rabbits were decreased compared with controls (p less than 0.01). When all animals were considered, relative glomerular filtration rate, estimated from 1/serum creatinine, was positively correlated with the T/M PAH and Kf. When only experimental animals were studied, 1/serum creatinine and T/M PAH were also correlated. Decreased glomerular filtration rate and dysfunction of proximal tubules were also correlated with abnormal tubule histology. We suggest that injury to glomeruli and tubules may represent independent manifestations of gentamicin toxicity. Dysfunction may be present even when there are only mild histologic changes and glomerular filtration rate is near normal. Kf does not appear to limit glomerular filtration rate after treatment with gentamicin; rather, some direct or indirect effect of tubular injury may determine the decrement in glomerular filtration rate.     

Heterogeneities in Consumer Diet Quality and Health Outcomes of Consumers by Store Choice and Income

Obesity and other diet-related health conditions have received much attention in the public health literature over the past two decades. This study investigates the relationship between household food budget shares at different food outlets with diet quality and weight-related health outcomes in the United States. Our analysis used event-level food purchase data from the national household food acquisition and purchases survey (FoodAPS). We find that, after controlling for observables, food purchase location is significantly associated with diet quality and body mass index (BMI). Our findings indicate that larger food budget shares at convenience stores and restaurants are linked with poor diet quality based on the healthy eating index-2015 (HEI-2015) scores and higher BMI. We further explored potential heterogeneity on outcomes of interest across income groups. Results suggest heterogeneous effects may exist across income groups: low-income households, who spent a larger share of their food budget at convenience stores and fast-food restaurants are related to poor diet quality and more likely to be obese. Our findings will help improve understanding of the causes of diet-related health problems and may illuminate potential avenues of intervention to address obesity.     

Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania

Background There is limited information about the clinical characteristics, treatment and outcome of maintenance hemodialysis patients with COVID-19. Moreover, regional differences are also conceivable since the extend and severity of outbreaks varied among countries.Methods In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 37 maintenance hemodialysis patients (median age 64 years, 51% men) hospitalized with COVID-19 from 24 March to 22 May 2020 as confirmed by real-time PCR.Results The most common symptoms at admission were fatigue (51%), fever (43%), dyspnea (38%) and cough (35%). There were 59% mild/moderate patients and 41% severe/critical patients. Patients in the severe/critical group had a significantly higher atherosclerotic burden since diabetic kidney disease and vascular nephropathies were the most common primary kidney diseases and eighty percent of them had coronary heart disease. Also, Charlson comorbidity score was higher in this group. At admission chest X-ray, 46% had ground-glass abnormalities. Overall, 60% patients received hydroxychloroquine, 22% lopinavir–ritonavir, 11% tocilizumab, 24% systemic glucocorticoids, and 54% received prophylactic anticoagulation. Seven (19%) patients died during hospitalization and 30 were discharged. The main causes of death were cardiovascular (5 patients) and respiratory distress syndrome (2 patients). In Cox regression analysis, lower oxygen saturation, anemia and hypoalbuminemia at admission were associated with increased mortality.Conclusions In conclusion, we observed a high mortality rate among maintenance hemodialysis patients hospitalized for COVID-19. Anemia, lower serum albumin and lower basal oxygen saturation at admission were factors associated with poor prognosis.