Sperm ubiquitination and DNA fragmentation in men with occupational exposure and varicocele

Assessment of sperm ubiquitination and DNA fragmentation as sperm functional markers are proposed to complement routine semen analysis. This study focuses on the evaluation of these markers in infertile men with varicocele or exposed to occupational background. The results were compared with normozoospermic men. Semen parameters in both groups were lower than those in the control group. Ubiquitination median, as a marker for functionality of the ubiquitin–proteasome system, was also lower in both groups. The ubiquitination median showed a significant positive correlation with motility in both groups, while it showed only a negative correlation with sperm morphology in the varicocele group. DNA fragmentation showed a significant correlation with semen parameters, in total varicocele and also total exposure groups. In conclusion, significant difference of sperm ubiquitination between normal and study groups further validates that sperm ubiquitination as a potential molecular marker for sperm evaluation in addition to routine semen analysis in clinical laboratories.     

Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition

GABAergic interneuron hypofunction is hypothesized to underlie hippocampal dysfunction in schizophrenia. Here, we use the cyclin D2 knockout (Ccnd2^−/−) mouse model to test potential links between hippocampal interneuron deficits and psychosis-relevant neurobehavioral phenotypes. Ccnd2^−/− mice show cortical PV⁺ interneuron reductions, prominently in hippocampus, associated with deficits in synaptic inhibition, increased in vivo spike activity of projection neurons, and increased in vivo basal metabolic activity (assessed with fMRI) in hippocampus. Ccnd2^−/− mice show several neurophysiological and behavioral phenotypes that would be predicted to be produced by hippocampal disinhibition, including increased ventral tegmental area dopamine neuron population activity, behavioral hyperresponsiveness to amphetamine, and impairments in hippocampus-dependent cognition. Remarkably, transplantation of cells from the embryonic medial ganglionic eminence (the major origin of cerebral cortical interneurons) into the adult Ccnd2^−/− caudoventral hippocampus reverses these psychosis-relevant phenotypes. Surviving neurons from these transplants are 97% GABAergic and widely distributed within the hippocampus. Up to 6 mo after the transplants, in vivo hippocampal metabolic activity is lowered, context-dependent learning and memory is improved, and dopamine neuron activity and the behavioral response to amphetamine are normalized. These findings establish functional links between hippocampal GABA interneuron deficits and psychosis-relevant dopaminergic and cognitive phenotypes, and support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.Precursors of most γ-aminobutyric acid (GABA)-releasing interneurons of the cerebral cortex and the hippocampus originate in the embryonic medial ganglionic eminence (MGE) (1–3). A subpopulation of MGE-derived cells differentiates into fast-spiking, parvalbumin-expressing (PV⁺) interneurons that tightly regulate the activity and synchronization of cortical projection neurons (2, 4). Structural and functional deficits in PV⁺ interneurons are hypothesized as a pathophysiological mechanism in schizophrenia and psychotic disorders (4–6).Although psychotic disorders are clearly heterogeneous in etiology, disinhibition within temporolimbic cortical circuits is postulated as a core pathophysiology underlying positive symptoms (e.g., delusions and hallucinations) and a subset of cognitive disturbances that manifest with psychosis (4, 5, 7). Postmortem studies of brains from individuals with psychotic disorders show reduced molecular markers of the number and/or function of PV⁺ interneurons in the hippocampus (6, 8). Consistent with these observations, basal metabolic activity in the hippocampus, as measured with functional magnetic resonance imaging (fMRI), is increased in schizophrenia, a phenotype that predicts psychosis and positive symptom severity (5, 7). This abnormal resting activity is postulated to underlie abnormal recruitment of hippocampal circuits during cognitive performance (5, 9). Striatal dopamine (DA) release capacity is also increased and correlated with positive symptoms in schizophrenia and its risk states (10, 11). Importantly, hippocampal hyperactivity may contribute to DA dysregulation (12), because rodent studies show that caudoventral hippocampal (in the primate, anterior hippocampal) efferents regulate the activity of DA neurons and medial striatal DA release (13, 14).Thus, converging evidence implicates hippocampal disinhibition in the abnormal striatal DA transmission and cognitive impairment in schizophrenia. However, the role of hippocampal inhibitory interneurons in psychosis-relevant circuitry remains to be established. To this end, we used the cyclin D2 (Ccnd2) knockout mouse model (15), which displays a relatively selective deficit in cortical PV⁺ interneurons, and transplantation of interneuron precursors from the MGE to elucidate relationships between reduced hippocampal GABA interneuron function and multiple psychosis-relevant phenotypes, and to explore a novel treatment strategy for psychosis.     

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra‐abdominally, and are defined by EWSR1‐WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion‐positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6–25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma‐like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1‐WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1‐WT1 fusion provides a definitive diagnosis of DSRCT. Genome‐wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.     

Lucigenin-pyrogallol chemiluminescence for the multiple detection of pyrogallol,cobalt ion,and tyrosinase

Developing new, cheap, sensitive and selective chemiluminescence (CL) systems with multiple detection properties is still a big challenge for biological and environmental applications. Here, we report a new CL system having multiple detection applications (environmental and biological). The developed lucigenin-pyrogallol system gave an enhancement (190 times) over the conventional lucigenin-H₂O₂ CL system. Cobalt ion and tyrosinase can inhibit lucigenin-PG CL intensity. Based on these phenomena, we have developed new CL methods for the detection of pyrogallol (LOD = 0.94 μM), lucigenin (LOD = 0.42 μM), cobalt (LOD = 68 nM), and tyrosinase (LOD = 1.8 μg/mL). Furthermore, the developed system gave excellent recoveries in real samples within the range of 93.59–103.12% for the assay of pyrogallol, Co²⁺ and tyrosinase in coffee, lake water, and human plasma, respectively.     

Chemical composition and mechanisms underlying the spasmolytic and bronchodilatory properties of the essential oil of Nepeta cataria L.

Aim of the study

The study was aimed to investigate the chemical composition and pharmacological basis for traditional use of essential oil of Nepeta cataria L. (Limiaceae) (Nc.Oil) in gastrointestinal and respiratory disorders.

Materials and methods

Chemical analysis was carried out through GC-EIMS, ¹³C NMR and Kovats Retention Indices while pharmacological study was carried out in isolated tissues preparations.

Results

Four major components; 1,8-cineol (21.00%), α-humulene (14.44%), α-pinene (10.43%) and geranyl acetate (8.21%) were identified among the 27 compounds in Nc.Oil. In isolated rabbit jejunum, Nc.Oil, papaverine and verapamil inhibited spontaneous and high K⁺(80 mM) precontractions, as well as shifted the Ca⁺⁺ concentration–response curves (CRCs) to right, indicating calcium channel blocking activity. In isolated guinea-pig trachea, Nc.Oil and papaverine inhibited carbachol (1 μM) and K⁺ precontractions with similar potency, while verapamil was more potent against K⁺. Nc.Oil also potentiated isoprenaline inhibitory CRCs, similar to papaverine, indicating papaverine-like PDE inhibitor activity. In isolated guinea-pig atria, Nc.Oil caused cardiodepression at around 25–80 times higher concentrations, similar to papaverine.

Conclusions

These data indicate that Nepeta cataria possesses spasmolytic and myorelaxant activities mediated possibly through dual inhibition of calcium channels and PDE, which may explain its traditional use in colic, diarrhea, cough and asthma.     

Assessment of the response to chemotherapy in gestational trophoblastic neoplasia with vaginal metastases

Background and goals  This study is designed to survey gestational trophoblastic neoplasia with vaginal metastases (GTN + VM) manifestations, prognosis and chemotherapy response in order to consider appropriate chemotherapy regimen for these patients. There have been just a few studies about treatment of GTN + VM. Materials and methods  Patients with Stage III GTN with or without vaginal metastases who had referred to Vali-e-Asr Hospital during 1996–2006 have been selected to take part in this study and the size of metastases was measured. Then response and resistance to single and combination chemotherapy regimens have been compared in these two groups. The data were processed using SPSS system (release 10). Statistical analysis was done with X² to determine factors associated with complete clinical response. The level of significance was assigned at P < .05. Results  Forty-eight patients with stage III (with pulmonary metastases) GTN patients have been selected, 13 with vaginal metastases and 35 without vaginal metastases. Incidence of vaginal metastases in stage III was 26%. Metastases were mainly in distal part of vagina and suburethra. Chief complaint was severe hemorrhage in 25% of patients and was controlled by vaginal packing with just one exception. Group of vaginal metastases showed 66.6% resistance to first-line chemotherapy, compared to 28.6% in patients with no vaginal metastases (P-value = 0.010). Median of chemotherapy courses in low-risk vaginal metastatic patients was 5 (mean = 5.2), compared to three courses in the group without vaginal metastases. Resistance to single chemotherapy was significantly higher in GTN + VM versus GTN without VM patients and resistance was higher especially in patients with metastases with more than 3 cm (in diameter). Conclusions  Vaginal metastasis with more than 3 cm in diameter is an important prognostic factor in GTN patients. There have higher risks for severe hemorrhage and resistance to single agent chemotherapy, so in these patients combination chemotherapy, with no regard to staging and scoring, would be a better choice. An erratum to this article can be found at     

槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分（英文）

目的：研究槟榔子（Areca catechu）粗提取物中所含的抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分及其作用机制。方法：使用70%甲醇水溶液对槟榔子进行粗提取。使用生物发光血小板凝集仪在富血小板血浆中测定槟榔子粗提取物的抗血小板聚集作用,使用分光光度计在试管内测定槟榔子粗提取物对乙酰胆碱酯酶活性的抑制作用。检测槟榔子中的多种化合物以测定槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分。结果：槟榔子粗提取物能够抑制花生四烯酸、二磷酸腺苷、血小板活化因子、肾上腺素及钙离子载体引起的血小板聚集,尤其对二磷酸腺苷及钙离子载体引起的血小板聚集的抑制最为明显;槟榔子粗提取物能够显著抑制乙酰胆碱酯酶的活性。在所检测的槟榔子所含化合物中,只有儿茶素对肾上腺素引起的血小板聚集有显著的抑制作用,而这种抑制作用显著弱于槟榔子粗提取物,提示槟榔子中的其他成分参与了这种抑制作用;鞣酸、没食子酸、薯蓣皂苷元和异去甲槟榔次碱能够抑制乙酰胆碱酯酶的活性,其中鞣酸的抑制作用强于槟榔子粗提取物。结论：槟榔子中含有抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分,而发挥这些功效的确切成分有待进一步的研究证实。     

Effect of cooking and supplementation with different kinds of meats on the nutritional value of mash (Vigna mungo)

The study was conducted to determine the nutritional value of mash (Vigna mungo) in raw and cooked forms and as effected by supplementation with different kind of meat, i.e. poultry, mutton and beef at 10, 15 and 20% levels. Nutritional assessment of all mash-containing diets (without or with supplementation) was made by chemical analysis as well as through rat assay. Mash contained 23.83% protein. Cooking resulted in minor changes in nutrients. Mash had 1.79% lysine which was reduced by 35% on cooking. All other amino acids also showed losses during cooking. Protein efficiency ratio (PER) of diet containing raw mash was 1.9% and cooking improved it to 2.8%. True digestibility (TD) also showed a significant improvement. Supplementation of mash with different kinds of meat did not improve the PER significantly over unsupplemented diet containing cooked mash only. TD, however, was improved from 74.89% in cooked to 75.58-87.06% in supplemented diets. Similarly net protein utilization (NPU), as a result of meat supplementation, improved from 43.54% in cooked to 42.88%-51.96%. Higher PER, TD and NPU values were observed in diets containing mash supplemented with 20% level of different meats.