Reproduction in male swamp wallabies (Wallabia bicolor): puberty and the effects of season

This study describes pubertal changes in testes and epididymides and seasonal changes in the adult male reproductive organs and plasma androgen concentrations of the swamp wallaby (Wallabia bicolor). Pre-pubescent males had testes with solid seminiferous cords and spermatogenesis only to the stage of gonocytes. Their epididymides had empty lumina along their entire length. The testes of three males undergoing puberty had some lumen formation and mitotic activity. Their epididymides were similar in appearance to those of adult males but were entirely devoid of any cells within the lumen of the duct. Three other pubescent males showed full lumen formation in the testes and spermatogenesis up to the elongating spermatid stage. Their epididymides were similar in appearance to those of adult males but with no spermatozoa in the duct. However, cells of testicular origin were found in the lumen of the duct in all regions suggesting that testicular fluids and immature germ cells shed into the rete testes flow through the seminiferous tubules into the epididymis before the release of mature testicular spermatozoa. The weights of testes and epididymides of adult males showed no change throughout the year but prostate weight and plasma androgen concentrations varied significantly with season, with maximums in spring and summer and minimums in winter. The volume fraction of Leydig cells and seminiferous tubules was significantly lower in winter than in summer; but, despite this, maturing spermatozoa were found in the testes throughout the year. Females in the area conceived year-round, suggesting that seasonal changes in the male reproductive tract did not prevent at least some males from breeding throughout the year.     

Antichlamydial antibodies and citric acid in patients with chronic prostatitis

Introduction The aim of the study was to evaluate the correlation between the presence of anti-C. trachomatis (C.t.) antibodies in serum and expressed prostatic secretions (EPS) and the concentration of citric acid in patients with chronic prostatitis. Materials and Methods The study involved 34 men with chronic prostatitis. The leukocyte count, presence of anti-C.t. antibodies (IgA, IgG), and citric acid concentration were determined in the EPS. The serum was examined for IgM, IgA, and IgG anti-C.t. antibodies. Specific antibodies were determined using the EIA method. The concentration of citric acid was measured using the ultraviolet method. Results Inflammation of the prostate ( ≥ 10 PMN) was found in 61.8% of the patients. A reduction in citric acid concentration in the EPS was detected in 58.8% of the men. Specific serum antibodies were detected in 58.8% of the patients, including 23.5% with IgM, 32.4% with IgA, and 44.1% with IgG. In all patients, serum IgM and IgA antibody titers were low, while those of IgG antibodies were strongly positive in 46.7% of the patients. Anti-C.t. antibodies in the EPS were detected in 44.1% of the patients, including 32.4% with IgA and 35.3% with IgG. In contrast to serum, the titers of IgG antibodies in the EPS were low in all the patients, while those of IgA were strongly positive in 54.5% of cases. In patients with positive serological outcomes, 85% had reduced concentrations of citric acid. Conclusions The occurrence of anti-C.t. antibodies is usually accompanied by a decrease in the concentration of citric acid in the prostatic secretion.     

Physiologically based pharmacokinetic-quantitative systems toxicology and safety (PBPK-QSTS) modeling approach applied to predict the variability of amitriptyline pharmacokinetics and cardiac safety in populations and in individuals

The physiologically based pharmacokinetic (PBPK) models allow for predictive assessment of variability in population of interest. One of the future application of PBPK modeling is in the field of precision dosing and personalized medicine. The aim of the study was to develop PBPK model for amitriptyline given orally, predict the variability of cardiac concentrations of amitriptyline and its main metabolite—nortriptyline in populations as well as individuals, and simulate the influence of those xenobiotics in therapeutic and supratherapeutic concentrations on human electrophysiology. The cardiac effect with regard to QT and RR interval lengths was assessed. The Emax model to describe the relationship between amitriptyline concentration and heart rate (RR) length was proposed. The developed PBPK model was used to mimic 29 clinical trials and 19 cases of amitriptyline intoxication. Three clinical trials and 18 cases were simulated with the use of PBPK-QSTS approach, confirming lack of cardiotoxic effect of amitriptyline in therapeutic doses and the increase in heart rate along with potential for arrhythmia development in case of amitriptyline overdose. The results of our study support the validity and feasibility of the PBPK-QSTS modeling development for personalized medicine.     

Diatoma polonica sp. nov. — a new diatom (Bacillariophyceae) species from rivers and streams of southern Poland

Diatoma polonica, a species first observed in samples from the Western Carpathians river systems in southern Poland, is described as a species new to science. The new species status resulted from the fact that the dimensions of cells found did not fit any of the diagnoses given in the literature for the European Diatoma taxa established so far. The genus is rather species-poor, even when the entire Holarctic flora is taken into account. The new species is morphologically closest to Diatoma moniliformis Kützing, particularly with respect to the vague resemblance of the valve outlines and the presence of a rimportula in each valve pole. Further, more or less similar taxa are D. tenuis Agardh, D. problematica Lange-Bertalot and D. mesodon (Ehrenberg) Kützing, all distinguished, in addition to other specific characteristics, by the rimoportulae regularly present at only one valve pole. Characteristics of D. polonica are described and compared with those of other species based on light and scanning electron microscopy.     

RF ablation of longstanding persistent atrial fibrillation in patient with familial dilated cardiomyopathy

A vicious circle of interactions between dilated cardiomyopathy and longstanding persistent AF/AFL may cause symptoms of advanced congestive heart failure. In a 31-year-old patient with diagnosis of familial dilated cardiomyopathy and permanent AF lasting for five years, gradually decreased left ventricular ejection fraction (LVEF) and increased diameter of heart chambers - left ventricular diastolic dimension (LVdD) 7.7 cm, left atrium (LA) 5.4 cm, and LVEF 15% were noted. Pharmacological treatment was ineffective Successful RF ablation of AF/AFL substrate (CTI block, PVs isolation, CFAE ablation, roof and MIG line, CS applications) reversed symptoms of significant heart remodeling (LVdD 5.9 cm, LA 4.3 cm, LVEF 50%).     

A Continuous Correlation Between Intracranial Pressure and Cerebral Blood Flow Velocity Reflects Cerebral Autoregulation Impairment During Intracranial Pressure Plateau Waves

Background

In the healthy brain, small oscillations in intracranial pressure (ICP) occur synchronously with those in cerebral blood volume (CBV), cerebrovascular resistance, and consequently cerebral blood flow velocity (CBFV). Previous work has shown that the usual synchrony between ICP and CBFV is lost during intracranial hypertension. Moreover, a continuously computed measure of the ICP/CBFV association (Fix index) was a more sensitive predictor of outcome after traumatic brain injury (TBI) than a measure of autoregulation (Mx index). In the current study we computed Fix during ICP plateau waves, to observe its behavior during a defined period of cerebrovascular vasodilatation.

Methods

Twenty-nine recordings of arterial blood pressure (ABP), ICP, and CBFV taken during ICP plateau waves were obtained from the Addenbrooke’s hospital TBI database. Raw data was filtered prior to computing Mx and Fix according to previously published methods. Analyzed data was segmented into three phases (pre, peak, and post), and a median value of each parameter was stored for analysis.

Results

ICP increased from a median of 22–44 mmHg before falling to 19 mmHg. Both Mx and Fix responded to the increase in ICP, with Mx trending toward +1, while Fix trended toward ?1. Mx and Fix correlated significantly (Spearman’s R = ?0.89, p < 0.000001), however, Fix spanned a greater range than Mx. A plot of Mx and Fix against CPP showed a plateau (Mx) or trough (Fix) consistent with a zone of “optimal CPP”.

Conclusions

The Fix index can identify complete loss of cerebral autoregulation as the point at which the normally positive CBF/CBV correlation is reversed. Both CBF and CBV can be monitored noninvasively using near-infrared spectroscopy (NIRS), suggesting that a noninvasive method of monitoring autoregulation using only NIRS may be possible.     

The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells

Neonates and infants are susceptible to infection due to distinct immune responses in early life. Therefore, development of vaccine formulation and delivery systems capable of activating human newborn leukocytes is of global health importance. Poly[di(carboxylatophenoxy)phosphazene] (PCPP) belongs to a family of ionic synthetic polyphosphazene polyelectrolyte compounds that can form non-covalent interactions with protein antigens and demonstrate adjuvant activity in animals and in human clinical trials. However, little is known about their ability to activate human immune cells. In this study, we characterized the effects of PCPP alone or in combination with a model antigen (recombinant HIV-Gag (Gag)), on the maturation, activation and antigen presentation by human adult and newborn dendritic cells (DCs) in vitro. PCPP treatment induced DC activation as assessed by upregulation of co-stimulatory molecules and cytokine production. Studies benchmarking PCPP to Alum, the most commonly used vaccine adjuvant, demonstrated that both triggered cell death and release of danger signals in adult and newborn DCs. When complexed with Gag antigen, PCPP maintained its immunostimulatory characteristics while permitting internalization and presentation of Gag by DCs to HIV-Gag-specific CD4⁺ T cell clones. The PCPP vaccine formulation outlined here has intrinsic adjuvant activity, can facilitate effective delivery of antigen to DCs, and may be advantageous for induction of beneficial T cell-mediated immunity. Moreover, polyphosphazenes can further reduce cost of vaccine production and distribution through their dose-sparing and antigen-stabilizing properties, thus potentially eliminating the need for cold chain distribution.     

Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients: an Exploratory Analysis

Neurocritical Care - Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury...     

Evaluation of selected serum protein markers as early detectors of ovarian cancer

OBJECTIVE: an attempt to determine the value of the simultaneous quantization of osteopontin (OPN), insulin-growth factor II (IGF II), leptin, prolactin and CA 125 for early detection of ovarian cancer. MATERIALS AND METHODS: Prospective study of 69 women including: 15 females with ovarian cancer; 33 females with benign ovarian neoplasm; 21 disease-free females; The levels of IGF II, prolactin, leptin and CA 125 were determined in serum, while the level of OPN was checked in plasma. RESULTS: The concentrations of IGF II, leptin and prolactin do not let us distinguish among disease-free females, females with ovarian cancer and those with benign ovarian neoplasms on the basis of biochemical markers. The comparison of OPN and CA 125 levels showed significant differences in the concentrations of the biomarkers between disease-free females and females with ovarian cancer, as well as between females with benign ovarian neoplasms and females with ovarian cancer. The ROC curves for two groups: disease-free females and females with ovarian cancer, proved the diagnostic value of OPN and CA 125. CONCLUSIONS: The simultaneous quantization of OPN, IGF II leptin and prolactin has not been proved useful for the early detection of ovarian cancer. Statistically significant increase of OPN & CA 125 levels was noted in case of women with ovarian cancer diagnosed through microscopic examination. The analysis of ROC curves showed comparable diagnostic usefulness of both markers. Quantization of OPN may have an additional value for treatment monitoring of women diagnosed with ovarian cancer but with concentration of CA 125 within the reference value.