Chronic graft vs. host disease and hypogammaglobulinemia predict a lower immunological response to the BNT162b2 mRNA COVID-19 vaccine after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Due to the high mortality rate of COVID-19, the assessment of BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) efficacy in allogeneic hematopoietic stem cell transplant (HSCT) recipients is mandatory. PATIENTS AND METHODS: We conducted a single-center pilot study with the main objective of evaluating the immunogenicity of the BNT162b2 mRNA vaccine in 31 hematological patients who underwent hematopoietic stem cell transplantation within the previous 12 months and/or were affected by chronic graft-vs.-host-disease (cGVHD), by the assessment of antibody levels at 30-45 days after the second dose of vaccine. RESULTS: After the second dose of vaccine, 23 out of 31 patients (74%) showed a positive immune response. The presence of severe cGVHD or Ig deficiency identified 7 out of 8 (85%) of non-responders. The median absolute cluster of differentiation 19 (CD19) count was significantly lower in non-responders vs. responders (109/µl vs. 351/µl). Underlying pathology, comorbidities, type of donor, time intervals from transplant and cluster of differentiation 3/cluster of differentiation 4/cluster of differentiation 8 (CD3/CD4/CD8) subsets were not significantly associated with an effective immune response to vaccination. CONCLUSIONS: Despite the limited sample of patients enrolled, our findings suggest that hypogammaglobulinemia and cGVHD could be associated with poor humoral response to the BNT162b2.

New insights on metastrongyloid lungworms infecting cats of Sardinia, Italy.

In addition to the well-known Aelurostrongylus abstrusus (Strongylida: Angiostrongylidae), Troglostrongylus brevior (Strongylida: Crenosomatidae) has recently been diagnosed as a causative agent of bronco-pulmonary infections of cats in Spain and Italy. However, information concerning the impact of this species of lungworm on feline population is limited to a few case reports. From July 2011 to May 2013 an epidemiological survey was carried out on Sardinia island (Italy), where 107 individual faecal samples were examined by Baermann technique, and first-stage larvae were identified based on their morphology and characterization of molecular markers. The 29.9% (32/107) of cats examined were infested by broncho-pulmonary nematodes and, although A. abstrusus was the most frequently detected (n=27; 25.2%), larvae of T. brevior were also found (n=7; 6.5%). In addition, two cats (1.9%) were co-infested by both species. Overall metastrongyloid infection was higher in female cats (n=22; 38.6%) than in males (n=10; 20%) (χ(2)=4.39; p=0.036). The mean age of positive animals was 21.1 (±29.8) months, being infected animals from 2 months to 10 years of age. Of the 32 animals that scored positive for lungworms only 6 (18.8%) displayed a respiratory condition associated with lungworm infestations. Biomolecular characterization confirmed the morphological diagnosis of A. abstrusus. Positive samples that were identified at genus level as Troglostrongylus spp. were molecularly characterized as T. brevior. This study represents the first epidemiological survey on metastrongyloid lungworms of domestic cats in Sardinia and the first report of T. brevior on this island.

Effect of acute cigarette smoking, alone or with alcohol, on gastric barrier function in healthy volunteers.

BACKGROUND: Smoking is a risk factor for gastroduodenal ulcer and gastric adenocarcinoma. However, the pathophysiological mechanisms induced by acute cigarette smoking in the human gastric mucosa are poorly understood. AIM: To evaluate the effect of acute cigarette smoking, alone or with alcohol, on the gastric permeability to sucrose, a specific marker of mucosal damage in the stomach. SUBJECTS AND METHODS: Twenty healthy volunteers (8 smokers/12 non-smokers) were studied. Each fasted subject ingested 500 ml of a 20% sucrose solution and the amount of sucrose excreted in a 5-hour urine collection was measured by gas chromatography Four sucrose permeability tests were carried out: 1. basal, 2. while smoking 5 cigarettes, 3. after drinking 50 ml of a 40 degrees alcoholic beverage, 4. a combination of 2+3. RESULTS: Sucrose excretion increased after alcohol ingestion (40.5 +/- 6.0 mg vs 143.1 +/- 28.9 mg, p = 0.002), but was not modified by acute cigarette smoking (34.4 +/- 5.9 mg). When alcohol and cigarettes were simultaneously consumed, the increase in alcohol-induced sucrose excretion was significantly reduced (73.1 +/- 16.6 mg, p = 0.03). Basal sucrose excretion was similar in smokers and non-smokers. However, in acute cigarette smoking, a decrease in sucrose excretion was observed in smokers (p = 0.02) but not in non-smokers. CONCLUSIONS: These results indicate that acute cigarette smoking may tighten the gastric mucosa in habitual smokers and this is associated with a smaller increase of gastric permeability induced by alcohol.

Effects of cocaine and morphine in rats from two psychogenetically selected lines: a behavioral and brain dialysis study.

The Swiss sublines of Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats differ in their reactivity to environmental and pharmacological stressors, in their sensitivity to stereotypies elicited by dopamine (DA)-mimetic agents, and in their densities of D1 DA receptors in the terminal field of the mesoaccumbens DAergic projection, an important link in the neural networks involved in the motor effects and reinforcing properties of drugs abused by humans. The present study was therefore designed to compare the behavioral and neurochemical effects of cocaine (5 mg/kg, i.p.) and morphine (0.5 mg/kg, s.c.) in RHA/Verh and RLA/Verh rats. To this aim, we measured motor activity and DA output in the nucleus accumbens as determined by brain microdialysis. The number of counts corresponding to horizontal, vertical, and total motor activities accumulated in basal conditions during the 60-min acclimation period was significantly larger in RHA/Verh than in RLA/Verh rats. Moreover, horizontal, vertical, and total motor activities throughout the 120-min observation period that followed the administration of vehicle tended to be larger in RHA/Verh rats, although the difference between the two lines was not statistically significant. In RHA/Verh rats, locomotion, rearing, and total motor activity were significantly more intense after acute cocaine and morphine challenges than after vehicle administration, whereas no significant differences in motor activity were observed between control and cocaine- or morphine-treated RLA/Verh rats. No line-related differences were detected in the basal DA output, but the effect of cocaine on DA release was more robust in RHA/Verh rats. Likewise, the effect of morphine was more pronounced in RHA/Verh than in RLA/Verh rats. Because the mesoaccumbens DAergic pathway plays a central role in the acquisition of motivational valence by environmental and pharmacological stimuli and, therefore, in operant behavior, our results suggest that comparative behavioral and neurochemical studies in these two lines may provide useful information on the biological correlates of drug dependence.

Anticonvulsant effect of felbamate in the pentylenetetrazole kindling model of epilepsy in the rat.

The present study was designed to examine the ability of felbamate, a novel antiepileptic agent, to antagonize the increase in seizure severity (i.e., chemical kindling) produced by chronic treatment with initially subconvulsant doses of pentylenetetrazol (PTZ). Rats were treated with PTZ (30 mg/kg, i.p., three times a week) for 8 consecutive weeks. Two other groups of rats received felbamate (300 or 400 mg/kg, i.p.), 90 min before each dose of PTZ. Pretreatment with felbamate at either dose prevented the progression of rank of seizures during chronic treatment with PTZ. Thus, the mean seizure score by the end of the chronic treatment (0-5 scale) was 0 in vehicle treated controls, 3.3 in rats treated with PTZ alone, 1.5 in rats treated with PTZ plus felbamate (300 mg/kg, i.p.) and 0.9 in the group treated with PTZ plus felbamate (400 mg/kg, i.p.). Felbamate also antagonized the long-term increase in the sensitivity to the convulsant effects of GABA function inhibitors observed in PTZ-kindled rats. Thus, the administration of a challenge dose of isoniazid (120 mg/kg, s.c.), picrotoxin (1.5 mg/kg, i.p.) or PTZ itself (15 mg/kg, i.p.), 15 to 45 days after the end of the chronic treatment regimen, induced convulsions in > 80% of PTZ-kindled rats and in < 20% of rats treated with PTZ + felbamate (400 mg/kg). The results are discussed in terms of the multiple mechanisms that can contribute to the anticonvulsant action of felbamate in the PTZ kindling model of epilepsy.

Pentylenetetrazol-induced kindling in rats: effect of GABA function inhibitors.

The repeated administration of subconvulsant doses of pentylenetetrazol (PTZ) produced a progressive sensitization to the effects of this compound (i.e., chemical kindling) in the rat. A very similar time-course for PTZ-induced kindling was observed using two different treatment schedules: 1) one injection every day (30 mg/kg, IP), and 2) one injection (30 mg/kg, IP) every second day. When these treatment schedules were used for eight consecutive weeks, more than 80% of the rats displayed convulsions by the end of treatment. In contrast, only 20% of the rats were sensitized if PTZ was administered twice daily at the dose of 15 mg/kg, IP. The increased sensitivity to the convulsant effect of PTZ was still present one year after completion of the chronic treatment. Moreover, rats kindled with PTZ showed an enhanced susceptibility to convulsions induced by different inhibitors of central GABAergic function, such as the chloride channel blocker picrotoxin, the benzodiazepine receptor ligands FG 7142 and Ro 15-4513, and the inhibitor of GABA synthesis isoniazid. In contrast, the sensitivity to the convulsant action of the glycine receptor antagonist strychnine was unchanged by repeated PTZ administration. It is suggested that kindling produced by PTZ may be associated with a persistent reduction in the inhibitory function of the GABAergic system in the brain.