Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group‐ and strain‐specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross‐reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains. J. Med. Virol. 69:579–587, 2003. © 2003 Wiley‐Liss, Inc.     

Kava-Kava administration reduces anxiety in perimenopausal women

OBJECTIVE: Disturbances of mood, such as anxiety and depression, increase in the perimenopausal period. Hormone replacement therapy or neuroactive drugs represent useful treatments for these disturbances but may be contraindicated or not accepted. Herein it was investigated the efficacy of Kava-Kava, an extract of Piper Methysticum, on mood of perimenopausal women. DESIGN: A 3-months randomized prospective open study investigating in perimenopausal women modifications induced by calcium supplementation (control; n=34), calcium plus Kava-Kava at the dose of 100 mg/day (n=15) or calcium plus Kava-Kava at the dose 200 mg/day (n=19). Anxiety was evaluated by the State Trait Anxiety Inventory (STAI); depression by the Zung's scale (SDS), and climacteric symptoms by the Greene's scale. Evaluations were performed at baseline and after 1 and 3 months. RESULTS: In the control group during the 3 months, anxiety, depression and climacteric symptoms tended to decline, but not significantly. During Kava-Kava anxiety declined (P<0.001) at 1 (-3.8+/-1.03) and 3 (-5.03+/-1.2) months, depression declined at 3 months (-5.03+/-1.4; P<0.002) and climacteric score declined (P<0.0006) at 1 (-2.87+/-1.5) and 3 (-5.38+/-1.3) months. Only the decline of anxiety induced by Kava-Kava was significantly greater than that spontaneously occurring in controls (P<0.009). CONCLUSIONS: The present data indicate that, in perimenopausal women, administration of Kava-Kava induces an improvement of mood, particularly of anxiety.     

Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.     

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric and adult population: a systematic review and meta-analysis

Neurosurgical Review - Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety,...     

The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61–15.04) and 11.55 (95% CI, 8.91–14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38–2.11) and 1.42 (95% CI, 0.49–2.36), and of all-cause death was 4.06 (95% CI, 2.50–5.61) and 3.96 (95% CI, 2.41–5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs–treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Effects of capsaicin,tachykinins, calcitonin gene-related peptide and bradykinin in the pig iris sphincter muscle

Summary Capsaicin-sensitive sensory neurons of the rabbit iris, by releasing tachykinins, exert a major role in the control of pupil motility in response to various noxious stimuli. However, the contribution of sensory innervation to the regulation of iris smooth muscle tone in other mammals species is not known. We have studied the effects produced by electrical field stimulation, capsaicin, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and bradykinin in the isolated iris sphincter muscle of the pig.Capsaicin (10 M): a) contracted the isolated sphincter muscle and; b) released immunoreactivity for substance P (SP-LI) and CGRP (CGRP-LI) from this preparation. These two effects were no longer observed at the second exposure to the drug. Electrical field stimulation (10 Hz, 60 V, 0.5 ms for 5 s) produced a biphasic contractile response. The rapid component was inhibited by atropine (1 M), while the delayed response was blocked by previous exposure to capsaicin (10 M).Substance P and neurokinin A consistently produced contraction of the pig iris sphincter muscle, substance P being more potent than neurokinin A. CGRP induced a contractile response in more than 50% of the preparations. The tachykinin antagonist [D-Argl, D-Trp^7,9, Leu¹¹-substance P (3 M) blocked: a) the effect of substance P (1 nM); b) the delayed response to electrical field stimulation and; c) reduced by more than 50% response to capsaicin. Bradykinin (10 M) failed to release either SP-LI or CGRP-LI. The contractile response evoked by bradykinin was unaffected by in vitro pretreatment with capsaicin (10 M).The existence in the pig iris of capsaicin-sensitive sensory fibres releasing neuropeptides and thus regulating sphincter muscle tone is proposed. Send offprint requests to Dr. P. Geppetti at the above address     

Surgery: Adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics

To evaluate the prevalence and risk factors for adenomyosis,the clinical records of consecutive women undergoing hysterectomyduring a 3 year period were retrieved. Data were collected onindication for the intervention, general sociodemographic characteristicsof the patients, age at menarche, parity, abortions, and menopausalstatus at surgery. Adenomyosis was diagnosed in 332 of the 1334cases (24.9%). The condition was present in 146 of the 627 patients(23.3%) with fibroids and menorrhagia, 68 of the 265 (25.7%)with prolapse, 21 of the 98 (21.4%) with ovarian cysts, 19 ofthe 100 (19%) with cervical cancer, 31 of the 110 (28.2%) withendometrial cancer, 16 of the 57 (28.1%) with ovarian cancer,and 19 of the 77 (24.7%) with miscellaneous indications. Thesedifferences were not statistically significant (x²₆ = 11.14).In comparison with nulliparous women, the odds ratio was 1.3and 1.5 respectively in women with one and two births (x²₁ trend= 5.76, P < 0.05). No relationship was found between ageat surgery, age at menarche, indications for surgery, menopausalstatus at intervention, and presence of endometriosis. Our findingsdo not support the notion that adenomyosis is more frequentlyrelated to particular clinical conditions, and suggest thatparity may be associated with an increased frequency of adenomyosis.     

Propagation of impulses in the guinea-pig ureter and its blockade by calcitonin gene-related peptide (CGRP)

The guinea-pig ureter was placed in a three-compartment organ bath to enable the application of electrical stimuli or drugs to its renal end (R site), the middle region (M-site) or the bladder end (B-site) while recording mechanical activity at the R- and B-sites. All experiments were performed in ureters pre-exposed to capsaicin (10 M for 15 min) to prevent the release of sensory neuropeptides from afferent nerves. Electrical field stimulation (EFS, 5–25 ms pulse width, 20 V) produced a phasic contraction at the site of stimulation (direct response to EFS) which propagated to the other end of the ureter. Section of the ureter at the M-site abolished the propagated response to EFS; after section, EFS applied at the M-site induced a phasic contraction at both the R-and B-sites. Likewise, the application of KCl at the M-site produced phasic contractions at both the R- and B-sites. Tetrodotoxin (1 M), nifedipine (1 M) or Bay K 8644 (1 M) applied at the M-site had no influence on the direct or propagated responses to EFS; nifedipine (10 M) applied at the M-site abolished the propagated responses without affecting the direct responses to EFS. Bay K 8644 (1 M) applied at the R-site produced a marked enhancement of the direct response (EFS applied at R-site) while having no effect on the amplitude of the propagated response to EFS. Nifedipine (1 M), applied at the R-site, produced a graded, time-dependent, inhibition of the direct response (EFS applied at R-site) and eventually suppressed it; the propagated response was unaffected until suppression of the direct response, when an allor-none blockade of the propagated response was observed. When applied at the B-site (EFS at Rsite), 1 M nifedipine produced a graded, time-dependent, inhibition of the propagated response and eventually suppressed it, without affecting the direct response to EFS. For further pharmacological analysis of drug action on the propagated activity, EFS was applied at the R-site and drugs were applied at the M-site. Human CGRP (CGRP, 0.1 M) or cromakalim (1-3 M) were applied in superfusion at the M-site in the absence or presence of glibenclamide (1 M). Neither drug affected the direct response to EFS; both CGRP and cromakalim produced a reversible suppression of the propagated response. Glibenclamide suppressed the inhibitory activity of 1 M cromakalim and partly antagonized the effect of CGRP; the blockade by glibenclamide was partly overcome by 3 M cromakalim. The present findings are consistent with the idea that propagation of excitation occurs because of the spread of electrical activity between smooth muscle cells of the ureter and that conduction of impulses is independent of local changes in contractility. The present results also demonstrate that CGRP induced a conduction block along the ureter and that this effect involves activation of glibenclamide-sensitive K channels. Therefore, a local release of CGRP in response to pathophysiological stimuli is, in principle, capable of suppressing ureteral peristalsis and antiperistalsis.     

Adoptive Immunotherapy With Tumor-Infiltrating Lymphocytes and Subcutaneous Recombinant Interleukin-2 Plus Interferon Alfa-2a for Melanoma Patients With Nonresectable Distant Disease: A Phase I/II Pilot Trial

Background: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-2a), for patients with metastatic melanoma.Methods: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6–18 × 10⁶ IU/m²/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-2a was administered subcutaneously at 3 × 10⁶ IU three times each week until progression.Results: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 × 10⁹ (range, 1–43 × 10⁹), and the median period of culture was 52 days (range, 45–60). rIL-2 was administered at doses ranging between 6 and 18 × 10⁶ IU/m²/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2–35%).Conclusions: Outpatient treatment with TIL plus rIL-2 and rIFN-2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.     

Comparison of CGS 15943, ZM 241385 and SCH 58261 as antagonists at human adenosine receptors

Three structurally related non-xanthine compounds, CGS 15943, ZM 241385 and SCH 58261, are potent A_2A adenosine receptor antagonists and have been used as tools in many pharmacological studies. We have now characterized their affinity and selectivity profile on human adenosine receptors stably transfected into either CHO cells (A₁ and A_2B receptors) or HEK-293 cells (A_2A and A₃ receptors). In binding studies using [³H]SCH 58261 as a radioligand, the three compounds were equally potent at A_2A receptors, their K _i value being less than 1 nM. Affinity for A₁ and A₃ receptors was measured using [³H]DPCPX and [¹²⁵I]AB-MECA as radioligands. Given the lack of selective ligands, interaction with A_2B receptors was assessed using the cAMP accumulation assay following stimulation by the adenosine receptor agonist N-ethylcarboxamidoadenosine (NECA). CGS 15943 was almost as potent at A₁ receptors (K _i 3.5 nM) as at A_2A receptors, showed moderate affinity for A₃ receptors (K _i 95 nM) and also interacted with A_2B receptors (K _i 44 nM; pA₂ 7.5). ZM 241385 showed little affinity for A₁ receptors (K _i 255 nM), and did not interact with A₃ receptors (K _i>10 μM); however, it displayed moderate affinity for A_2B receptors (K _i 50 nM; pA₂ 7.3). SCH 58261 had weak affinity for A₁ receptors (K _i 287 nM), no interaction with A₃ receptors (K _i>10 μM), and showed negligible interaction with A_2B receptors (K _i 5 μM; pA₂ 6.0). These data indicate that SCH 58261 is the most selective A_2A antagonist currently available. Moreover, the different receptor selectivity of these three chemically related compounds provides useful information to progress with structure-activity relationship studies. Received: 2 July 1998 / Accepted: 6 October 1998