Efficacy of hydrogen peroxide wipes for decontamination of AZD1222 adenovirus COVID-19 vaccine strain on pharmaceutical industry materials.

This study aimed to evaluate the performance of accelerated hydrogen peroxide® wipes (HPW) for decontamination of the chimpanzee adenovirus AZD1222 vaccine strain used in the production of recombinant COVID-19 vaccine in a pharmaceutical industry. Two matrices were tested on stainless-steel (SS) and low-density-polyethylene (LDP) surfaces: formulated recombinant COVID-19 vaccine (FCV) and active pharmaceutical ingredient (API). The samples were spiked, dried and the initial inoculum, possible residue effect (RE) and titre reduction after disinfection with HPW were determined. No RE was observed. The disinfection procedure with HPW resulted in complete decontamination the of AZD1222 adenovirus strain in FCV (≥7·46 and ≥7·49 log10 infectious unit [IFU] ml-1 for SS and LDP carriers respectively) and API (≥8·79 and ≥8·78 log10 IFU ml-1 for SS and LDP carriers respectively). In conclusion, virucidal activity of HPW was satisfactory against the AZD1222 adenovirus strain and can be a good option for disinfection processes of SS and LPD surfaces in pharmaceutical industry facilities during recombinant COVID-19 vaccine production. This procedure is simple and can be also applied on safety unit cabins and sampling bags made of LDP as well.

Orexin expression is regulated by alpha-melanocyte-stimulating hormone.

The hypothalamic melanocortin system plays a fundamental role in the regulation of energy homeostasis. Orexins (hypocretins) are also involved in a diverse range of physiological processes, including food intake. Previous evidence has suggested that hypothalamic orexin expression may be influenced by the central melanocortin system. Here, we studied orexin mRNA levels in pro-opiomelanocortin-deficient (Pomc(-/-)) mice, a mouse model lacking all endogenously produced melanocortin peptides. Orexin expression in the lateral hypothalamus was significantly increased in corticosterone deficient Pomc(-/-) mice. Furthermore, when circulating glucocorticoids were restored to levels within the physiological range, orexin expression remained elevated. However, i.c.v. administration of the melanocortin alpha-melanocyte-stimulating hormone (MSH) to Pomc(-/-) mice reduced orexin expression back down to wild-type levels. This was independent of the effects of alpha-MSH on food intake because elevated orexin expression persisted in Pomc(-/-) mice pairfed to alpha-MSH-treated animals. These data indicate that alpha-MSH may play a role in the regulation of orexin expression in Pomc(-/-), with an elevation in orexin levels contributing to the hyperphagia seen in these animals.

Analysis of the cytokine profile in spleen cells from dogs naturally infected by Leishmania chagasi.

Recent studies suggest that asymptomatic dogs infected with canine visceral leishmaniasis (CVL) develop a Th1 immunological profile whilst oligosymptomatic and symptomatic CVL-infected animals present a Th2 profile. In the present study, an RT-PCR method has been standardised and employed to evaluate the frequency and the semi-quantitative level of expression of the cytokines IL-4, IL-10, IL-12, INF-gamma and TNF-alpha in splenocytes of 30 dogs naturally infected with Leishmania chagasi and of 7 non-infected dogs (NID). An increase in the level of expression of IL-12 (p=0.059) was detected in all CVL-infected dogs compared with NID. In dogs exhibiting high parasitism, the frequency of expression of IL-10 was higher (p=0.011) than in animals presenting low parasitism or medium parasitism (MP) and in NID animals, whilst the level of expression of IL-10 was higher (p=0.0094) than in animals exhibiting MP and in the NID group. Positive correlations between the levels of expression of IL-10 with respect to the progression of the disease (IL-10: r=0.3510; p=0.0337) and the levels of expression of IL-10 and INF-gamma increase in parasitism (IL-10: r=0.3428; p=0.0438 and INF-gamma: r=0.4690; p=0.0045) were observed. Such data suggest that CVL is marked by a balanced production of Th1 and Th2 cytokines, with a predominant accumulation of IL-10 as a consequence of an increase in parasitic load and progression of the disease, and INF-gamma was related with the increase in parasitic load.

Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy.

BACKGROUND: The role that growth factors and their receptors play in human cancer growth and progression makes them interesting targets for novel treatment modalities. Our approach consisted of active immunotherapy with the epidermal growth factor (EGF). Two pilot clinical trials were conducted to examine the safety and immunogenicity of a five-dose immunization protocol and to compare different adjuvants and treatment designs. PATIENTS AND METHODS: Forty patients with advanced non-small-cell lung cancer were enrolled in both trials. They were randomized to be treated with aluminum hydroxide or montanide ISA 51 as adjuvants in the EGF vaccine preparation. The use of cyclophosphamide prevaccination treatment was evaluated in the second trial. RESULTS: Pooled data from both trials showed that the use of montanide as adjuvant increased the percentage of good antibody responders (GAR). Cyclophosphamide prevaccination treatment did not provoke improvements in antibody response. GAR had a significant increase in survival as compared with poor antibody responders. Response duration was also related to a significant improvement in survival rates. CONCLUSIONS: Vaccination with five doses of EGF vaccine is safe and immunogenic. Montanide ISA 51 increased the percentage of GAR. There is a direct relationship between anti-EGF antibody titers and immune response duration with survival time.

Cardiovascular effects produced by nitric oxide-related drugs in the caudal ventrolateral medulla.

The role of nitric oxide in the central control of blood pressure was evaluated by interfering with its local formation in the caudal region of the ventrolateral medulla (CVLM). Urethane anesthetized male Wistar rats were used. Microinjection of L-arginine (L-Arg, 25-100 nmol) produced a hypertensive effect without significant changes in heart rate (HR). Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME, 7.4 nmol) produced a significant hypotensive effect. Microinjection of L-Arg (50 nmol) combined with L-NAME (7.4 nmol) did not significantly change mean arterial pressure or HR. A similar finding was obtained with microinjection of L-Arg (50 nmol) 5 min after microinjection of methylene blue (5 nmol) into the CVLM. The pressor effect of L-Arg was also abolished by prior i.v. injection of a vasopressin V1 receptor antagonist, but not by prior i.v. injection of prazosin. These results suggest an inhibitory role for local NO in the CVLM and that nitrergic pathways at the CVLM participate in the central regulation of AVP release.

Performance of deaf children using ear-level and body-worn hearing aids.

Profoundly deaf children (N: 37, aged 61/2-8 yrs) received intensive audiological work-ups in 1974. In addition, they received a speech discrimination test (WIPI) and a Question Comprehension Task. Of these Ss, 15 were using ear-level and 22 were using body-worn aids. Mean unaided audiograms of children wearing the two kinds of aid did not differ. Ear-level aids improved tested hearing significantly more than did body aids. In addition, children wearing ear-level aids scored significantly higher on the WIPI (visual and combined auditory-visual conditions) and on the Question Task, compared to children wearing body aids.