Adaptations in skeletal muscle capillarity following changes in oxygen supply and changes in oxygen demands

Summary The effects of changes in oxygen supply and oxygen demands on fiber cross-sectional areas, capillary dersities and capillary to fiber ratios were determined in three skeletal muscles of rat. The muscles examined were the vastus lateralis, soleus, and diaphragm. Reduced oxygen supply was produced by subjecting rats to ambient hypoxia, and increased oxygen demands were produced by subjecting rats to low ambient temperatures or treatment with thyroxin. Capillaries were visualized by injecting fluorescent dyes into the circulation. Muscles were quick frozen at resting lengths to preserve normal fiber geometry and were subsequently sectioned on a cryostat. All of the muscles sampled from animals in the experimental groups had elevated capillary densities. However, capillary to fiber ratios were not increased significantly in any muscle, for any experimental condition. Thus, all of the observed differences in capillarity were due to changes in the intrinsic rate of muscle fiber growth. Further, the relations of capillary density and capillary to fiber ratio to fiber area were the same as those obtained during normal maturation, suggesting that capillary growth is closely linked to the intrinsic rate of fiber growth.     

The carbamate insecticide ZZ-Aphox® induced structural changes of gills,liver, gall-bladder,heart, and notochord of Rana perezi tadpoles

Embryos of Rana perezi were kept under laboratory conditions and treated with carbamate ZZ-Aphox^® at chronic doses of 0.02 and 0.14 for 9 weeks. Both the histological study and the analysis of mortality show a direct relationship between the dosage and the effects of the pesticide. The histological study of the survivors over 56 days show damages in gills, liver, gall-bladder, heart, and notochord. Damages on the epithelia of gills (on their distal portion) and gall-bladder recover over a few days, whereas those provoked on the compacting of the hepatic parenchyma and the hepatocytes, the auricle and the perinotochordal collagenic fibers alter their structure in a lasting way. Potentials of such alterations are discussed, with special reference to the possible interference of the pesticide on the successful synthesis of the supporting connective sheaths.     

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.     

Sex selection may be inadvertently performed in in-vitro fertilization--embryo transfer programmes

The present study aims to ascertain whether sex selection maybe inadvertently performed in human in-vitro fertilization (IVF)and embryo transfer (IVF-embryo transfer) programmes when selectingfor high quality embryos (those with the fastest cleaving ratesand/or the best morphology) at the fresh transfer cycle. Allpatients entering into the study were treated with gonadotrophinsafter pituitary suppression with gonadotrophin-releasing hormoneagonists (GnRHa) and had intrauterine embryo transfer on day2 post-insemination. These patients were retrospectively dividedinto three groups according to whether the difference in meannumber of cells between embryos transferred and all embryosavailable for transfer in a given cycle was less than (negativeselection), equal to (no selection) or greater (positive selection)than zero. In cycles resulting in singleton births, the sexratio of the resulting babies was significantly (P 0.005) shiftedtoward the female (88.8%) and to the male (90.0%) in the negativeand positive selection groups respectively. No shift in sexratio was observed in cycles resulting in multiple births. Maternalage was another independent factor affecting sex ratio at birth.Sex ratio was significantly (P 0.05) skewed in favour of males(62.7%) and females (71.4%) in women <35 and 235 years ofage respectively. Maternal age, number of embryos transferredand the event of selecting or not selecting the slowest cleavingembryos for transfer were entered automatically in a three-groupdiscriminant model for distinguishing cycles resulting in onlyboys, both boys and girls, and only girls. These data suggestthat (i) sex selection may be inadvertently performed in IVF-embryotransfer programmes when selecting for high quality embryosat the fresh transfer cycles; (ii) human endometria may be favourable,indifferent or hostile to either fast cleaving or slow cleavingembryos depending on maternal age; and (iii) ‘natural’sex selection may be performed for social, psychological ormedical reasons.     

Influence of DNA Delivery Method on Gene Targeting Frequencies in Human Cells

Gene targeting can be used for genetic studies of human cell lines and has significant potential for somatic cell gene therapy. These applications are however restricted by the low frequency of homologous recombination in higher eukaryotes compared to the relatively efficient nonhomologous integration of transfected DNA into the genome. As part of our attempts to overcome this problem, we compared two widely used transfection methods for their efficiency in gene targeting. To our surprise we found that, for conditions that render similar frequencies of nonhomologous integrants, lipofection is much less efficient than electroporation in generating targeted clones. This suggests that nonhomologous and homologous recombination have different requirements for DNA delivery in human cells.     

Gastro-Gastric Fistulas and Marginal Ulcers in Gastric Bypass Procedures for Weight Reduction

Background: Gastro-gastric fistulas and marginal ulcers are frequent and serious complications of gastric compartmentalization procedures for obesity. Methods: The authors analyzed 810 patients after 911 operations for gastro-gastric fistulas and marginal ulcers over an 8-year period. All patients underwent a form of gastric bypass, in which a pouch is constructed along the lesser curvature of the stomach. The outlet of the pouch was restricted with a prosthetic band. In the first 189 patients (Group I), the pouch and stomach were stapled in continuity or partially divided. In the next 222 patients (Group II), segments were stapled and separated by transection. In the remaining 492 cases (Group III), in addition to transection of the stomach, a limb of jejunum was interposed between the pouch and excluded stomach. Stapled anastomoses were done in Group I and II patients and a portion of Group III patients. The remaining patients underwent hand-sewn anastomosis. Results: Gastro-gastric fistulas occurred in 49% of the patients in Group I, 2.6% of those in Group II, and 0% of those in Group III. In stapled anastomosis, the incidence of marginal ulceration in Groups I, II, and III were 8.5%, 5.4%, and 5.1%, respectively. In a subset of Group III patients, in whom a two-layer, hand-sewn anastomosis was done, the incidence was 1.6% when the outer layer was not absorbable and 0% when both layers were absorbable. Conclusions: Gastro-gastric fistulas and marginal ulcerations are likely the result of breakdown of the mucosa resulting from migrating staples and other foreign material. Lack of integrity of the gastric lining facilitates the action of the gastric digestive process. Transection of gastric segments with interposition of jejunum prevents gastro-gastric fistula formation. An intact serosa appears to block the digestion of bowel wall by gastric enzymes. Our early data suggest that the use of absorbable sutures at the gastrojejunostomy significantly decreases the incidence of marginal ulceration.     

Combining Clozapine with ECT

We describe the safe and effective use of the combination of clozapine and ECT in a patient with schizophrenia who had lost responsiveness to clozapine alone. We suggest further investigation to define the role of combined clozapine-ECT treatment in the management of treatment-resistant schizophrenia.     

Obesity Surgery Poly-parametric Patient Auto-evaluation

A simple auto-evaluation sheet is presented for the proper assessment of the patient's condition after surgery. Stress is put not only on weight loss, but on other important factors as well.