Dermatoglyphic characterization of Berbers from Morocco: qualitative and quantitative digital and palm data

BACKGROUND: The demographic impact of the Arabization in the Berber genetic background has been extensively studied by means of different classical and DNA genetic markers. Information from other biological traits as dermatoglyphics could be of interest in order to gain an insight into the relationship between these two North African groups. AIM: The Moroccan Berber population is characterized by means of digital and palm dermatoglyphics to determine the degree of genetic affinities among Berber and other Mediterraneans, especially the Moroccan Arab-speakers. Subjects and methods: Finger patterns, pattern intensity, finger total ridge counts, pattern frequencies in the five configuration areas of the palm, mainline D terminations, and a-b ridge count were analysed in a sample of 120 males and 103 females of Moyen Atlas (Morocco). RESULTS: Bilateral asymmetry was more pronounced than sexual differences in the overall distribution of the analysed traits. Our two series (males and females) exhibit high values of total ridge count (TRC) and mainline D terminations in comparison with other Mediterranean series. Several pattern frequencies in fingers and palm areas also differentiate the Berbers of Moyen Atlas from North Africans. CONCLUSION: The picture obtained by principal components based on qualitative digital and palm data revealed that Berber males were within the variation range of North African groups while Berber females clustered with some Iberian samples. The population pattern obtained in a bivariate plot of quantitative finger data showed the Berbers (males and females) as the most differentiated population in the Mediterranean context. Dermatoglyphic data failed to indicate any particular proximity between Berbers and Arab-speakers from Morocco.     

Classical polymorphisms in Berbers from Moyen Atlas (Morocco): genetics,geography, and historical evidence in the Mediterranean peoples

BACKGROUND: Mediterranean population relationships have recently been reviewed through the analysis of classical and DNA markers. The differentiation between Berbers and Arabic-speakers to the south, and the genetic impact of the seven centuries of Muslim domination in the Iberian Peninsula have been among the most interesting questions posed in these studies. AIM: The present study seeks to assess the degree of genetic affinity between the two main population groups of Morocco: Berbers and Arabic-speakers. Data from the Berber study population were also compared with published information on 20 circum-Mediterranean groups. SUBJECTS AND METHODS: A Berber sample of 140 individuals from Moyen Atlas (Morocco) has been characterized using 15 classical markers (ABO, Duffy, MNSs, Rh, ACPl, AKl, ESD, GLOI, 6-PGD, PGMl, GC, HP, PI, PLG and TF). RESULTS: Allele frequencies in the Berbers fit well into the general southern Mediterranean ranges, albeit with some peculiarities, such as the high FY*A, ACPl*C, and PI*S values. The general pattern of relationships among Mediterranean peoples tested by genetic variance analysis was compatible with a north-south geographical differentiation. Spatial auto-correlation analysis in the different geographical regions of the Mediterranean reveals that the highest degree of association between allele frequencies and geographical distances corresponds to the western (41% of significant correlograms) and northern Mediterranean populations (33%). When only southern Mediterranean groups were considered, the degree of geographical structure considerably decreases (11% of significant correlograms). CONCLUSIONS: The different loci studied revealed close similarity between the Berbers and other north African groups, mainly with Moroccan Arabic-speakers, which is in accord with the hypothesis that the current Moroccan population has a strong Berber background. Differences in the spatial pattern of allele frequencies also are compatible with specific population histories in distinct Mediterranean areas, rather than general population movements across the whole region.     

Prevention of transfusion-associated graft-versus-host disease: selection of an adequate dose of gamma radiation

To determine the optimal dose of gamma radiation necessary to inhibit T- lymphocyte function and prevent transfusion-acquired graft-versus-host disease (TA-GVHD), a donor plateletpheresis component was initially divided into ten 20-mL samples. One sample was not irradiated, while the other nine samples were treated with gamma radiation at doses ranging from 500 to 4500 cGy. T-lymphocyte function was subsequently measured by mixed lymphocyte cultures and mitogen stimulation assays. The results were assessed in each test by calculating the percentage of inhibition of each irradiated sample as compared to that of the unirradiated sample. The accuracy of the delivered dose of gamma radiation was measured with thermoluminescent dosimeters. It was concluded that a nominal dose of 3000 cGy (actual dose delivered, 2898 cGy) is the appropriate amount of gamma radiation needed to eliminate T- lymphocyte-mediated graft-versus-host disease.     

高效液相色谱法测定人血清和尿中盐酸青藤碱浓度及药代动力学研究

用RP-HPLC法,以三唑仑为内标,反相C₁₈为分析柱,乙腈—0.01mol·L^-1磷酸二氢钠—四甲基乙二胺(46∶54∶0.22v/v)为流动相,磷酸调至pH6.9,检测波长263nm,测定血清和尿中盐酸青藤碱浓度,线性范围分别为6～480ng·mL^-1和0.06～3μg·mL^-1,平均回收率75.88%和91.35%,日内日间误差小于5%,最低检测浓度血清4ng·mL^-1,尿40ng·mL^-1。8名健康男性志愿者单次口服盐酸青藤碱片80mg,测定血清及尿浓度,该药符合二室开放模型,体内消除符合一级动力学消除过程,主要药代动力学参数:T_1/2α0.791±0.491h,T_1/2β9.397±2.425h,T_{max 1.040±0.274h,Cmax246.604±71.165ng·mL^-1,AUC 2651.158±1039.050ng·h·mL^-1,CL 0.033±0.01ng·mL^-1。}     

Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta-oxidation enzymes and peroxisome proliferation in rats treated with dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific differences

Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male and female sex hormones in the adrenal cortex of man. In livers of rats and mice DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation enzymes associated with peroxisome proliferation. Prolonged treatment of rats with DHEA induces liver tumors that are more frequent in females arising mainly in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol. 23, 591-605, 1995). Because of paucity of information on hepatic zonation of peroxisomal response to DHEA and controversial reports on gender-specific differences of its effects the present study was undertaken using qualitative immunohistochemical and quantitative immunoelectron microscopical techniques in addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal beta- oxidation enzymes, which by quantitative analysis was equally strong in male and female animals, whilst catalase and urate-oxidase were not increased. Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than in female rats. Immunohistochemistry confirmed the induction of cytochrome P450 IVA showing a marked lobular gradient in female animals with strong induction in pericentral and almost no induction in periportal regions of the liver lobule. In male animals cytochrome P450 IVA was expressed more uniformly across the liver lobule. A similar sex specific zone-dependent response was observed for peroxisomes. DHEA induced in females a significant zonal gradient with marked peroxisome proliferation and a strong induction of peroxisomal hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in periportal regions. Livers of male animals, in contrast, showed a uniform peroxisomal proliferation to DHEA with only slight zonal differences. The striking homologies of the induction patterns of cytochrome P450 IVA and the peroxisome proliferation in both sexes support the notion of a functional relationship. In view of the almost exclusive periportal localization of DHEA-induced tumors in female rats in contrast to the pericentral localization of the peroxisomal proliferation shown by this study, it seems likely that other factors in addition to peroxisome proliferation may contribute to the hepatocarcinogenic effect of DHEA.      

Effectiveness,safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.     

Deficient prepulse inhibition induced by selective breeding of rats can be restored by the dopamine D2 antagonist haloperidol

Deficient sensorimotor gating, measured as prepulse inhibition (PPI) of startle, reflects disturbed information processing found in neuropsychiatric disorders. Examining the ability to selectively breed rats for high and low PPI, results showed significant differences of PPI scores within two generations. Comparing antipsychotics to restore PPI of the low group, haloperidol was shown more effective than clozapine. This suggests low PPI rats may be useful models for neuropsychiatric disorders and screening antipsychotics.     

Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.