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.     

Effects of selective vegetative denervation on the urinary bladder of the adult rat

The present work is a study of the plastic capacity of the peripheral nervous system subjected to different aggressions in the case of 28 rats of the Wistar breed. They were divided into four groups: 1) sympathetic deafness (n=9); 2) parasympathetic deafness (n=9); 3) evaluation of regeneration (n=9); 4) control group (n=5). An image analyser was used to study the acetylcholinesterase (AChE) and Tyrosine Hydroxylase (TH) positive ganglionic neurones of the pelvic ganglion (GP) as well as the dorsal ganglions (GRD) compared with the control group. With group 3 a study was also made of the possible plasticity of the transacted axons using a wheat germ agglutinin conjugated-horseradish peroxidase (WGA-HRP) neurotracer. The statistical study was carried out by means of the analysis of variance (ANOVA), Fisher test and Scheffe method, with a p<0.05 taken as significant. The results show the predominant role of the pelvic nerve in the modulation of the plastic changes produced at the ganglionic level, with a lesser influence of the hypogastric nerve. Further studies are needed in order to define the specific role of each of these in the act of miction.     

Injection of irradiated b16 melanoma genetically-modified to secrete IFN-alpha causes regression of an established tumor

Highly aggressive murine B16 melanoma was engineered to secrete IFN-alpha constitutively. Cells expressing IFN-alpha were injected into syngeneic C57BL/6 mice and the mice were monitored for tumor development. Secretion of IFN-alpha by B16 melanoma cells completely abrogated their tumorigenicity in syngeneic mice. LFN-alpha-secreting cells also abrogated the tumorigenicity of IFN-gamma-secreting and TNF-alpha-secreting cells when injected in combination whereas cells secreting either IFN-gamma or TNF-alpha grow progressively in mice when injected alone. Moreover, protected animals developed significant immunity against subsequent challenge with parental cells. Injection of parental cells and IFN-alpha-secreting cells together in a mixed tumor transplantation assay resulted in a significant reduction of tumorigenicity of the parental cells. Histopathological studies of the tissues from the injection site of the mice inoculated with a combination of parental and B16.IFN-alpha cells revealed the existence of a massive cellular infiltrate composed of lymphocytes and granulocytes at an early stage (7-11 days). In the later stages (22 days), no recognizable tumor tissue was detected. Injection of irradiated IFN-alpha-secreting cells in the mice carrying an established tumor completely prevented tumor development in 80% of the treated mice when injection was performed on the same side as the tumors. Injection of irradiated IFN-alpha-secreting cells in the contralateral site showed much less effect on the established tumor. Systemic antitumor effects on the established tumor can be enhanced by using a combination of irradiated IFN-alpha and IFN-gamma secreting cells as a vaccinating inoculum.     

Brain uptake of iodinated L-meta-tyrosine, a metabolically stable amino acid derivative

The possibility of using L-meta-tyrosine (L-mTyr) with high metabolic stability and amino acid transport affinity was evaluated. mTyr was first separated into D- and L-isomers with high-performance liquid chromatography and both were labelled with non-carrier-mediated 125I. Biodistribution and pharmacological studies of radioiodinated mTyr in mice and rats were then performed. 125I-L-mTyr showed greater accumulation in the brain and the pancreas. It accumulated in the brain stereospecifically in the in vivo studies and by the L-tyrosine competitive energy dependent transport system in the in vitro studies. It was resistant to deiodination, appeared to have no retention mechanism and was rapidly excreted. 123I-L-mTyr has the potential of an amino acid transport marker, especially in the brain and the pancreas.     

Meningeal carcinomatosis in bladder tumor

We report a strange case of a bladder whose first metastasic manifestation, after two years of the diagnosis, was a peripheric polyneuropathia. This patient was treated with immunotherapy with BCG for superficial carcinoma of the bladder during one year. Gradually central neurological symptoms appeared and the patient died one month later. A meningeal carcinomatosis was identify as the cause. No bone metastases existed, which is the most frequent way of tumours extension towards leptomeninges. We argue about the way to arrive at meninges.     

Long term survival in metastatic nephroblastoma. A case report.

We describe a case of metastatic nephroblastoma presenting as renal rupture. Histology was "favorable". Lung metastases were discovered early during follow-up. Radiotherapy and surgical excision were therefore combined with intensive chemotherapy. Ten years later, the patient is symptom-free.     

Prosthetic arteriovenous fistula for vascular access in hemodialysis.

Vascular access through subcutaneous prosthetic arteriovenous fistulas was studied in eighteen dogs. Dacron velour and woven Dacron grafts (6 mm diameter) were constructed across the lower abdomen between the common femoral artery and the opposite common femoral vein. In heparinized animals 197 percutaneous punctures were made with a "14 guage hemodialysis cannula at weekly intervals. Over a period of one and a half years there was no instance of infection. One of the fourteen Dacron velous and all four woven Dacron fistulas thrombosed. These data suggested the feasibility of achieving repetitive blood access through Dacron velour vascular prostheses. Nineteen Dacron velour fistula bypasses between the brachial artery and median basilic vein were performed in fifteen selected patients for a total dialysis period of ninety-six months. Failed standard subcutaneous fistulas or absence of suitable vessels in the upper extremity were indications for the primary procedure. Of three looped forearm fistulas, two thrombosed at twenty-two and two months. Complications among sixteen straight bypasses in the arm included two graft infections and one cannula tract infection. There were no instances of thrombosis in this group. The advantages of single needle dialysis in these high risk patients have been emphasized. Eleven grafts are presently functioning two to nine months postoperatively. Our preliminary results suggest that a Dacron velour fistula merits consideration as an alternative for vascular access in maintenance hemodialysis.     

Effects of cocaine in rats exposed to heroin.

We investigated whether chronic exposure to heroin alters responses to cocaine in ways that might explain the use of cocaine by opioid addicts. To this end, the effects of cocaine (5 and 20 mg/kg) were assessed on locomotor activity of rats chronically exposed to heroin (0.0, 3.5, 7.0, and 14.0 mg/kg/day, over 14 days, via osmotic mini-pumps), or withdrawn from heroin (1 day, acute withdrawal, and 14 days, protracted withdrawal). Chronic heroin exposure, in itself, dose dependently increased locomotion and acute cocaine administration further elevated locomotor activity in a dose-dependent and additive manner. During acute withdrawal, there was a dose-dependent decrease in locomotion that was reversed by cocaine in a dose-dependent manner. During protracted withdrawal, spontaneous locomotion normalized, but rats previously exposed to heroin displayed cross-sensitization to cocaine as indicated by small, but significant, enhanced locomotor response to 5 mg/kg of cocaine, and enhanced intravenous self-administration of low doses of cocaine (0.13 mg/kg/infusion). In a separate study, we measured extracellular dopamine (DA) in the nucleus accumbens (Acb) using in vivo microdialysis before and after acute withdrawal from heroin. During chronic exposure to heroin, basal extracellular DA was elevated dose dependently, whereas in acute withdrawal, levels were not different from those in vehicle-treated rats. In response to cocaine, however, DA activity in the Acb was significantly lower in rats withdrawn from the highest dose of heroin.