Regucalcin, a calcium-binding protein with a role in male reproduction?

Regucalcin (RGN) is a calcium (Ca(2+))-binding protein which plays an important role in the regulation of Ca(2+) homeostasis and has been shown to catalyse an important step in L-ascorbic acid biosynthesis. It is encoded by an X-linked gene and differs from other Ca(2+)-binding proteins by lacking the typical EF-hand Ca(2+)-binding domain. RGN controls intracellular Ca(2+) concentration by regulating the activity of membrane Ca(2+) pumps. Moreover, RGN has been indicated to regulate the activity of numerous enzymes and to act in the regulation of cell proliferation and apoptosis. The importance of Ca(2+) homeostasis in spermatogenesis has been demonstrated by several studies, and its disruption has been shown to cause reversible male infertility. Recently, the expression of RGN in male reproductive tissues has been described and its localization in all testicular cell types was demonstrated. In addition, RGN expression is regulated by androgens, a class of steroid hormones recognized as male germ cell survival factors and of uttermost importance for spermatogenesis. Altogether, available information suggests the hypothesis that RGN might play a role in spermatogenesis, directly or as a mediator of androgen action. This review discusses this hypothesis presenting novel data about RGN expression in human testis.     

Entomological characteristics of malaria transmission in Manhiça, a rural area in southern Mozambique

From October 1997 to September 1998, an entomological survey was carried out in Manhi?a, Mozambique, to describe the anopheline population and intensity of malaria transmission. Ten different huts were randomly selected for entomological surveillance throughout the year. CDC light trap collections were conducted during three nights each month. Additional knockdown spraying catches were carried out in the morning, after the last catch. A total of 17,245 Culicinae and 1,251 Anophelinae were collected during the study. There was substantial house to house variation and seasonality in the distribution of Anophelinae population, with a peak in April towards the end of the warm and rainy season. Four species of genus Anopheles (Diptera: Culicidae) were described: Anopheles funestus Giles, Anopheles tenebrosus D?nitz, Anopheles arabiensis Patton, and Anopheles merus D?nitz. An. funestus constitutes 72.3% of the anopheline population. The estimated sporozoite rate was 1.2% and the average entomological inoculation rate for the area was 15 infective bites per person per year.     

Functional autoantibodies, a new paradigm in autoimmunity?

The recent detection of stimulatory autoantibodies as a characteristic feature of systemic sclerosis (scleroderma), established the presence of such autoantibodies as a characteristic pathophysiologic finding in a second classical autoimmune disease after autoimmune thyroid disease. This observation raises the possibility of a new paradigm in abnormal autoimmune function, the presence of stimulatory (and suppressive), functional autoantibodies as characteristic features of abnormal autoimmune function. The assumption of such a paradigm opens interesting new research avenues within rheumatology and in other medical specialty areas. Within reproductive medicine, and akin to the concept of hypo- and hyperthyroidism, the possible juxtaposition of polycystic ovarian syndrome (PCOS) and premature ovarian aging (POA), as opposite abnormalities of adrenal function, under control of autoimmune adrenal antibodies, deserves further investigation.     

Culture-positive invasive aspergillosis in a medical center in Taiwan, 2000–2009

We reviewed 776 patients who were culture positive for Aspergillus species at the hospital from 2000 to 2009. The isolates were collected for species identification by oligonucleotide hybridization and sequence analysis. A total of 96 cases of proven or probable IA were identified according to published criteria. The incidence of IA has increased significantly during the study period. Aspergillus fumigatus and A. flavus (41.7% each) were equally prevalent causative species. IA due to unusual species including A. nidulans (n=2), A. versicolor (n=2), and A. tubingensis (n=1) were also found. Among patients with IA, 55.2% had hematological disorder, 19.8% had underlying lung disorder, and 10.4% had autoimmune disease. The isolates species (P<0.001) and underlying disease (P<0.001) significantly affect the association of a positive culture with invasive disease. The overall mortality at three months was 62.5%, which remained stable throughout the study period. Multivariate analysis identified prior steroid use (P=0.007) as a significant risk factor for death, while surgery (P=0.030) and voriconazole (P=0.012) had protective effects. In conclusion, autoimmune disorders and underlying pulmonary diseases should also be considered as important predisposing factors of IA. Further emphasis on surgery and voriconazole in the management of IA might be beneficial.     

Antiallergic Function of KR62980, a Peroxisome Proliferator-Activated Receptor-γ Agonist,in a Mouse Allergic Rhinitis Model

Purpose

Peroxisome proliferator-activated receptor γ (PPAR-γ) has been shown to play an important role in the control of inflammatory responses acting on macrophages, mast cells, T cells and eosinophils. A novel PPAR-γ ligand, KR62980 have been recently focused on due to the lower undesirable effects than other PPAR-γ ligands such as rosiglitazone and pioglitazone. The present study was aimed to investigate the effects of KR62980 on nasal symptoms and immunopathological profiles in allergic nasal mucosa in murine allergic rhinitis model.

Methods

BALB/c mice were sensitized and challenged intranasally with ovalbumin (OVA). KR62980 was administered intraperitoneally or orally 3 hours before each intranasal OVA challenge.

Results

Administration of KR62980 significantly decreased the number of nasal rubbing, nasal sneezing, ova-specific IgE and total IgE in serum, secretion of Interleukin (IL)-4, IL-5, and IL-17 from the spleen and eosinophilic infiltration in the nasal mucosa. KR62980 decreased the expression of IL-4, IL-5 and IL-10 mRNAs in the nasal mucosal tissue, while, it elevated the level of IL-10 and IFN-γ in splenocyte culture. KR62980 seemed to decrease IL-17 level in local and systemic level even though it did not reach to statistical significance. The anti-inflammatory effect was more definite when the KR62980 was administered intraorally than intraperitoneally.

Conclusions

A novel PPAR-γ ligand, KR62980 can attenuate OVA-induced allergic inflammation in mice mainly through modulation of Th2 cytokines. This finding suggests that PPAR-γ might have a role in the treatment of allergic rhinitis.     

β-Caryophyllene,a natural sesquiterpene,modulates carbohydrate metabolism in streptozotocin-induced diabetic rats

The study was designed to evaluate the antihyperglycemic effects of β-caryophyllene (BCP), a natural sesquiterpene from spices on streptozotocin (STZ) induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40 mg/kg b.w.) in adult male Wistar rats. Diabetic rats exhibited an increase in glucose and HbA_1c with a significant fall in insulin and hemoglobin levels. Aberrations in carbohydrate metabolic enzymes were noticed in liver, kidney and skeletal muscle of diabetic rats. A fall in liver and skeletal muscle glycogen with alterations in glycogen synthase and phosphorylase activities was also observed. Oral administration of BCP in dose dependent manner and glibenclamide (600 μg/kg b.w.), a standard oral hypoglycemic drug to diabetic rats for 45 days significantly decreased glucose with increased plasma insulin levels and ameliorated the altered activities of carbohydrate metabolic enzymes to near normal. The insulinotropic effect of BCP was supported by immunohistochemical studies. BCP at a dose of 200 mg/kg b.w. exerted significant antidiabetic effects than other two doses (100 and 400 mg/kg b.w.). We conclude that administration of BCP has beneficial effects in glucose homeostasis in diabetic rats.     

Mandibulofacial dysostosis,microtia, and limb anomalies in a newborn: a new form of acrofacial dysostosis syndrome?

Zhang Y, Dai Y, Liu Y, Ren J. Mandibulofacial dysostosis, microtia, and limb anomalies in a newborn: a new form of acrofacial dysostosis syndrome? The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders involving craniofacial dysostosis and limb anomalies. Depending on the type of limb defects, two major groups have been defined: Nager syndrome with predominant preaxial anomalies and Miller syndrome with postaxial malformations. Genomic copy number variation, a common type of genomic variability, can influence gene expression by disrupting coding sequences, perturbing long‐range gene regulation, or altering gene dosage, and these effects could contribute to phenotypic variations or disease risk. We present a distinct AFD case with mandibulofacial dysostosis, microtia and limb malformations but without limb defects, which may represent a new form of AFD. To investigate the etiology of the phenotype, whole genomic high‐resolution array comparative genomic hybridization analysis was carried out, revealing two cryptic duplications, 1p36.33 and 1q21.3‐q22 duplications. Two genes, VWA1 and PYGO2, contained in the two duplications, respectively, are likely to be the candidate genes for the phenotype of our patient.     

Neurodrinking: Is alcohol a substrate in a novel,endogenous synthetic pathway for norepinephrine?

A number of preclinical and clinical studies indicate multiple types of interaction between ethanol intake and the mood-related neurotransmitter, norepinephrine (NE). For example, ethanol interacts with dopamine beta-hydroxylase (DBH), an enzyme that plays an essential role in the only well-established endogenous synthetic pathway for NE, whereby dopamine is hydroxylated to form NE. While the DBH pathway may indeed be the only endogenous mechanism for producing NE, another possibility is that multiple means have evolved for the biosynthesis of this very important neurotransmitter, where some pathways may be independent of DBH. If so, such redundancy would provide greater assurance that enough NE is available for the body to use in this neurotransmitter's various physiological roles. This paper puts forth the hypothesis ethanol is a substrate in a novel, endogenous synthetic pathway for NE, consistent with some studies showing that intake of ethanol increases the concentration of endogenous NE. Also consistent with this hypothesis, the molecular structure of ethanol is a physical subset of the structure of NE itself. If the hypothesis is correct, it may have important implications for understanding the physiological basis of alcohol use, abuse, and dependence in humans, as well as modeling these phenomena in animals. Importantly, the hypothesis is directly testable in rodents by presenting ethanol to DBH knockout mice, which are thought to lack NE, and then measuring if NE is synthesized in these animals.     

Hot flushes in a male population aged 55, 65, and 75 years,living in the community of Linköping,Sweden

OBJECTIVE: Hot flushes are as common in castrated men as in menopausal women. We investigated whether hot flushes exist in a normal aging male population and to what extent. DESIGN: A questionnaire was sent to all men living in Link?ping, Sweden, who were 55, 65, and 75 years old ( = 1,885). The questionnaire asked for demographic data, medical history, mood status, medication, castrational therapy, and smoking, exercise, and alcohol habits, among other items. We asked specifically for current hot flushes unrelated to exercise or a warm environment. RESULTS: Of the questionnaires received, 1,381 were eligible for evaluation; 33 were analyzed separately because these men had been castrated. Hot flushes of any frequency were reported by 33.1% of noncastrated men, 4.3% reported flushes at least a few times per week, and 1.3% reported daily flushes. Half of the men reporting flushes were also bothered by them, ie, almost every sixth man in total. We found a relation between occurrence of hot flushes and other symptoms thought to be related to low testosterone concentration, such as decreased muscle strength or endurance, decreased enjoyment of life, sadness or grumpiness, and lack of energy ( < 0.05). CONCLUSIONS: Hot flushes occur in one third of a population of noncastrated older men, approximately half of whom consider flushes as bothersome. Neither the mechanisms nor whether the symptoms would respond to testosterone supplementation is known. Androgen substitution to treat symptoms possibly related to a male climacteric is still controversial. Studies are needed to evaluate the needs for and the effects of androgen treatment on vasomotor symptoms.     

Identification of a novel methicillin-resistant Staphylococcus aureus epidemic clone in Córdoba, Argentina, involved in nosocomial infections

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are increasingly a main health concern worldwide for hospitalized patients. In addition, the prevalence of community-acquired infection has risen continuously during the last few years. Some MRSA clones spread easier than others within the hospital environment and therefore are frequently implicated in outbreaks. Thus, the spread of a unique epidemic multiresistant clone, the so-called South American clone, is the main cause of nosocomial infections produced by this bacterium in Brazil and in some regions of Argentina, Chile, and Uruguay. In the present work we describe the identification of a novel clone of MRSA that is involved in nosocomial infections and that shows a prevalence as high as that for the South American clone. A total of 53 consecutive single-patient MRSA isolates were recovered during a 3-month period (May to July 1999) from six different hospitals (955 beds) in Córdoba. The isolates were initially typed according the antibiotic resistance and phage susceptibility patterns, followed by genotyping using pulsed-field gel electrophoresis (PFGE). PFGE analysis of the 53 MRSA isolates revealed six major types (A to F) and 25 subtypes. The B-type DNA pattern was indistinguishable from that of the South American epidemic clone observed in 34% of the isolates. A novel highly prevalent clone, showing the A-type DNA pattern and representing 38% of the isolates, was also identified. Moreover, the most frequent subtype of the A clonal family triggered an outbreak in a hospital 2 months later, further confirming its epidemic feature.     

Molecular epidemiology of Serratia marcescens in two hospitals in Gdańsk, Poland, over a 5-year period

The history of the Serratia marcescens population in two hospitals in Danzig, Poland, over a 5-year period was analyzed in a study that combined MIC evaluation, typing by randomly amplified polymorphic DNA (RAPD) analysis and pulsed-field gel electrophoresis, and analysis of extended-spectrum beta-lactamases (ESBLs). We analyzed 354 isolates collected from 341 patients in two teaching hospitals in Danzig, Poland, from 1996 to 2000. The antimicrobial susceptibility profiles varied greatly, and for resistance to newer beta-lactams, probable AmpC cephalosporinase derepression and ESBL production occurred in about 23 and 19% of the isolates, respectively. RAPD typing, by which 69 types were discerned altogether, revealed a high degree of clonal diversity among the populations. However, the four most prevalent types were highly predominant, grouping approximately 71% of the isolates studied. These clones were observed in the two hospitals and were strong contributors to both outbreaks and the background of endemicity of the S. marcescens infections. Some of the strains that were not so widely spread (12 RAPD types; approximately 14% of the isolates) were responsible for several smaller outbreaks, and the remaining isolates represented unique RAPD types (53 types; approximately 15% of the isolates) and were probably sporadic introductions from other environments. ESBLs were identified in several different clones, and some of these had most likely already been introduced into the hospitals as ESBL producers, whereas the others acquired the ESBL-encoding genes from other enterobacterial strains in these environments. The CTX-M-3 enzyme, which is widely observed in Poland, was the most common ESBL type among the S. marcescens isolates, followed by TEM-47 and SHV-5. The complex epidemiology of ESBLs, especially in 1999 and 2000, must have arisen from the introduction of ESBL producers from other centers, their clonal dissemination, and the constant penetration of the S. marcescens populations with plasmids with ESBL genes. Multiple S. marcescens isolates were obtained from 11 patients, who probably represented both patients with recolonizations and reinfections and patients with recurrences of infections with the evolution of the strain's susceptibility.     

Gender differences in drinking patterns and alcohol-related problems in a community sample in São Paulo, Brazil

OBJECTIVE:

To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking.

METHODS:

A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of São Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month non-heavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender.

RESULTS:

Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages.

CONCLUSIONS:

Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.     

Alterations in nitrogen metabolism in freshwater fishes, Channa punctatus and Clarias batrachus, exposed to a commercial-grade λ-cyhalothrin, REEVA-5

In the present study, two freshwater fishes Channa punctatus and Clarias batrachus were exposed to sub-acute concentrations of a commercial-grade λ-cyhalothrin, REEVA-5, for 96 h to observe the changes in amino acid catabolism under pyrethroid-induced stress and to investigate the comparative mechanisms of ammonia detoxification in both fishes. The experiments included the estimation of levels of free amino acid, urea, ammonia and the specific activities of aspartate aminotransferase (AAT), alanine aminotransferase (AlAT), glutamate dehydrogenase (GDH), glutamine synthetase (GS) and arginase in different vital organs of fishes. λ-cyhalothrin caused significant decline in the levels of amino acids along with simultaneous significant increase in the activity of AAT, AlAT and GDH, which indicated amino acid catabolism as one of the important mechanisms to meet out immediate energy demand of fishes. The level of ammonia was observed to be enhanced considerably at lower concentrations of λ-cyhalothrin while higher concentrations caused remarkable decline. The λ-cyhalothrin treatment resulted in significant increase in the activities of GDH and GS with concomitant increase in the activity of arginase and level of urea, indicating activation of two different mechanisms of ammonia detoxification. The mechanism of ammonia detoxification through its conversion into glutamate and glutamine was more prominent in C. punctatus, while C. batrachus demonstrated ureogenesis as the major route. In fishwise comparison, C. batrachus was observed to be more sensitive with respect to the above-mentioned parameters. Another important finding was that unlike the liver, the kidney appeared as one of the primary sites of ureogenesis in fishes.     

Breathing Resistance and Ultrafine Particle Deposition in Nasal–Laryngeal Airways of a Newborn, an Infant, a Child, and an Adult

As a human grows from birth to adulthood, both airway anatomy and breathing conditions vary, altering the deposition rate and pattern of inhaled aerosols. However, deposition studies have typically focused on adult subjects, results of which may not be readily extrapolated to children. This study numerically evaluated the age-related effects on the airflow and aerosol dynamics in image-based nose?Cthroat models of a 10-day-old newborn, a 7-month-old infant, a 5-year-old child, and a 53-year-old adult. Differences in airway physiology, breathing resistance, and aerosol filtering efficiency among the four models were quantified and compared. A high-fidelity fluid-particle transport model was employed to simulate the multi-regime airflows and particle transport within the nasal?Claryngeal airways. Ultrafine particles were evaluated under breathing conditions ranging from sedentary to heavy activities. Results of this study indicate that the nasal?Claryngeal airways at different ages, albeit differ significantly in morphology and dimension, do not significantly affect the total deposition fractions or maximum local deposition enhancement for ultrafine aerosols. Further, the deposition partitioning in the sub-regions of interest is different among the four models. Results of this study corroborate the use of the in vivo-based diffusion parameter (D ^0.5 Q ^?0.28) over the replica-based parameter in correlating nasal?Claryngeal depositions of ultrafine aerosols. Improved correlations have been developed for the four age groups by implementing this in vivo-based diffusion parameter as well as the Cunningham correction factor.     

Association of Variants in PPARγ2, IGF2BP2, and KCNQ1 with a Susceptibility to Gestational Diabetes Mellitus in a Korean Population

Purpose

Patients with gestational diabetes mellitus (GDM) have been reported to exhibit the same genetic susceptibility as that observed in those with type 2 diabetes mellitus (T2DM). Recent polymorphism studies have shown that several genes are related to T2DM and GDM. The aim of this study was to examine whether certain candidate genes, previously shown to be associated with T2DM, also offer a specific genetic predisposition to GDM.

Materials and Methods

The current study was conducted in 136 Korean pregnant women, who gave birth at Gil Hospital, from October 2008 to May 2011. These study subjects included 95 subjects with GDM and 41 non-diabetic controls. We selected the specific genes of PPARγ², IGF2BP2, and KCNQ1 for study and amplified them using the polymerase chain reaction. This was followed by genotyping for single nucleotide polymorphisms. We then compared the genotype frequencies between patients with GDM and non-diabetic controls using the χ² test. We obtained and analyzed clinical information using Student''s t-test, and statistical analyses were conducted using logistic regression with SPSS Statistics software, version 19.0.

Results

Significant differences were observed in maternal age, body mass index, weight gain and weight at time of delivery between the groups compared. Among pregnant women, polymorphisms in PPARγ² and IGF2BP2 were shown to be highly correlated with GDM occurrence, whereas no correlation was found for KCNQ1 polymorphisms.

Conclusion

Our results indicated that genetic polymorphisms could also be of value in predicting the occurrence and diagnosis of GDM.