Clinical severity of COVID-19 with omicron variant predominance in relation to vaccination status, age, comorbidities- a single center in Selangor, Malaysia.

INTRODUCTION: Recently, the rapid surge of reported COVID-19 cases attributed to the Omicron variant of severe acute respiratory syndrome coronavirus (SARS-CoV-2) created an immediate concern across nations. Local information pertaining to the new variant of concern (VOC) is lacking. We aimed to determine the clinical characteristics of COVID-19 during a period of Omicron prevalence among patients hospitalised from February 1 to 21, 2022 at Sungai Buloh Hospital and to estimate the risks of disease progression presumably caused by this variant in association with gender, age, comorbidity, and vaccination status. MATERIALS AND METHODS: In this retrospective, singlecentered, retrospective cohort study, all hospitalised adults with laboratory-confirmed COVID-19, aged 18 and above, were recruited from February 1 to 21, 2022. Clinical characteristics, investigations, and outcomes were assessed. RESULTS: A total of 2279 patients aged 18 years and above with laboratory-proven COVID-19 were recruited and analysed, excluding 32 patients owing to incomplete data. Majority of the study population had a mean age of 41.8 ± 17.7, was female-predominant (1329/2279, 58.6%), had completed a primary series of vaccination with a booster (1103/2279, 48.4%), and had no underlying medical conditions (1529/2279, 67.4%). The risk of COVID-19-related disease progression was significantly lower in hospitalised patients under the age of 50 who were female, had no comorbidity, and had completed two doses of the primary series with or without a booster. [respectively, OR 7.94 (95% CI 6.16, 10.23); 1.68 (1.34, 2,12); 2.44 (1.85, 3.22); 2.56 (1.65, 3.97), p< 0.001]. CONCLUSION: During the period of Omicron prevalence, a favourable outcome of COVID-19 was strongly associated with female gender, age below 50, a comorbidity-free condition, and having completed immunization. With this new observation, it could help improve public health planning and clinical management in response to the emergence of the latest VOC.

Genitourinary non-tuberculous mycobacterial (GU-NTM) infections: A single institution experience in South India.

INTRODUCTION: Non-tuberculous mycobacterial (NTM) infections are rarely reported, and more so with genitourinary infections. This retrospective study was designed to understand the proportion and behaviour of genitourinary non-tuberculous mycobacterial (GU-NTM) infections compared with genitourinary mycobacterial tuberculosis (GU-MTB) treated at a tertiary care hospital in South India. MATERIALS AND METHODS: The hospital records of every bacteriologically proved GU-MTB and GU-NTM infections treated at this centre from 2010 to 2016 were retrospectively reviewed. RESULTS: There were ten patients of GU-NTM and 15 patients of GU-MTB. There was no significant difference in presentation other than lesser frequency of irritative lower urinary tract symptoms (LUTS) among patients with GU-MTB. Urine smear for AFB was positive in 60% and 47% of GU-NTM and GU-MTB patients. 40% of GU-NTM patients had history of urinary tract instrumentation. Mycobacterium abscessus was grown in four patients and one had Mycobacterium fortuitum/chelonae complex; all the rest were rapid growers. No patient had multi-drug resistant tuberculosis. Imaging studies of GU-NTM patients were indistinguishable from GU-MTB with renal, ureteral and bladder involvements, and stone formation. The drug sensitivities varied among the NTM patients but all showed sensitivity to clarithromycin uniformly. Need for varieties of surgeries in the early and late phases were also comparable. CONCLUSIONS: GU-MTB and GU-NTM infections are indistinguishable from their clinical presentation and imaging studies. All cases of suspected genitourinary mycobacterial infections must be subjected to nucleic acid testing. Treatments based on clinical and radiological features without culture studies may misdiagnose GU-NTM infections as MDR GU-MTB, thereby delaying the appropriate treatment.

Reduced rotavirus vaccine efficacy in protein malnourished human-faecal-microbiota-transplanted gnotobiotic pig model is in part attributed to the gut microbiota.

The low efficacy of human rotavirus (HRV) vaccines in low- and middle-income countries (LMIC) remains a major challenge for global health. Protein-calorie malnutrition (kwashiorkor) affects the gut microbiota and compromises immune development, leading to environmental enteropathy, vaccine failures, and increased susceptibility to enteric diseases in young children. Relationship between diet and reduced vaccine efficacy in developing countries is not well established; therefore, we investigated the interconnections between the host-microbiota-nutrition-HRV vaccine using HRV-vaccinated, human infant faecal microbiota (HIFM)-transplanted neonatal gnotobiotic pigs fed with a protein deficient or sufficient diet. The microbiota from faecal, intestinal (duodenum, ileum, jejunum, and colon), and systemic tissue (liver, spleen, and mesenteric lymph node [MLN]) samples was analysed before and after HRV challenge using MiSeq 16S rRNA sequencing. Overall, microbiota from deficient fed HIFM pigs displayed, compared to the sufficient group, significantly higher Shannon index, especially in the faeces and lower intestines; higher level of Proteus and Enterococcus, and lower level of Bifidobacterium, Clostridium, and Streptococcus in the three types of samples collected (P<0.05); and higher unique operational taxonomic units (OTUs), especially in the systemic tissues. Further, the multivariate analysis between microbiota and immunologic data showed that 38 OTUs at the genus level correlated (r2≤0.5 or ≥-0.5; P<0.05) with at least one host immune response parameter (regulatory [Tregs and transforming growth factor-ß], effectors [interferon (IFN)-γ+ CD4+ and CD8+ T cells, IFN-γ and interleukin (IL)-12], and inflammatory [tumour necrosis factor-α, IL-17 and IL-22]) and with opposite trends between diet groups. Differences described above were increased after HRV challenge. We demonstrated that a protein deficient diet affects the composition of the gut microbiota and those changes may further correlate with immune responses induced by HRV and perturbed by the deficient diet. Thus, our findings suggest that the reduced efficacy of HRV vaccine observed in Gn pig model is in part attributed to the altered microbiota composition.

Cardiolipin, conformation, and respiratory complex-dependent oligomerization of the major mitochondrial ADP/ATP carrier in yeast.

The phospholipid cardiolipin has pleiotropic structural and functional roles that are collectively essential for mitochondrial biology. Yet, the molecular details of how this lipid supports the structure and function of proteins and protein complexes are poorly understood. To address this property of cardiolipin, we use the mitochondrial adenosine 5'-diphosphate/adenosine 5'-triphosphate carrier (Aac) as a model. Here, we have determined that cardiolipin is critical for both the tertiary and quaternary assembly of the major yeast Aac isoform Aac2 as well as its conformation. Notably, these cardiolipin-provided structural roles are separable. In addition, we show that multiple copies of Aac2 engage in shared complexes that are largely dependent on the presence of assembled respiratory complexes III and IV or respiratory supercomplexes. Intriguingly, the assembly state of Aac2 is sensitive to its transport-related conformation. Together, these results expand our understanding of the numerous structural roles provided by cardiolipin for mitochondrial membrane proteins.

Effect of antibiotic, probiotic, and human rotavirus infection on colonisation dynamics of defined commensal microbiota in a gnotobiotic pig model.

We developed a gnotobiotic (Gn) pig model colonised with defined commensal microbiota (DMF) to provide a simplified and controlled system to study the interactions between intestinal commensals, antibiotics (ciprofloxacin, CIP), probiotics (Escherichia coli Nissle 1917, EcN) and virulent human rotavirus (VirHRV). The DMF included seven gut commensal species of porcine origin that mimic the predominant species in the infant gut. Gn piglets were divided into four groups: DMF control (non-treated), DMF+CIP (CIP treated), DMF+CIP+EcN (CIP/EcN treated), DMF+EcN (EcN treated) and inoculated orally with 105 cfu of each DMF strain. The pig gut was successfully colonised by all DMF species and established a simplified bacterial community by post-bacteria colonisation day (PBCD) 14/post-VirHRV challenge day (PCD) 0. Overall, Bifidobacterium adolescentis was commonly observed in faeces in all groups and time points. At PCD0, after six days of CIP treatment (DMF+CIP), we observed significantly decreased aerobic and anaerobic bacteria counts especially in jejunum (P<0.001), where no DMF species were detected in jejunum by T-RFLP. Following HRV challenge, 100% of pigs in DMF+CIP group developed diarrhoea with higher diarrhoea scores and duration as compared to all other groups. However, only 33% of pigs treated with EcN plus CIP developed diarrhoea. EcN treatment also enhanced the bacterial diversity and all seven DMF species were detected with a higher proportion of Bifidobacterium longum in jejunum in the DMF+CIP+EcN group on PBCD14/PCD0. Our results suggest that EcN increased the proportion of B. longum especially in jejunum and mitigated adverse impacts of antibiotic use during acute-infectious diarrhoea. The DMF model with a simplified gut commensal community can further our knowledge of how commensals and probiotics promote intestinal homeostasis and contribute to host health.

Retention and relapse in clinical practice.

Maintaining teeth in their corrected positions following orthodontic treatment can be extremely challenging. Teeth have a tendency to move back towards the original malocclusion as a result of periodontal, gingival, occlusal and growth related factors. However, tooth movement can also occur as a result of normal age changes. Because orthodontics is unable to predict which patients are at risk of relapse, those which will remain stable and the extent of relapse that will occur in the long-term, clinicians need to treat all patients as if they have a high potential to relapse. To reduce this risk, long term retention is advocated. This can be a significant commitment for patients, and so retention and the potential for relapse must form a key part of the informed consent process prior to orthodontic treatment. It is vital that patients are made fully aware of their responsibilities in committing to wear retainers as prescribed in order to reduce the chance of relapse. If patients are unable or unwilling to comply as prescribed, they must be prepared to accept that there will be tooth positional changes following treatment. There is currently insufficient high quality evidence regarding the best type of retention or retention regimen, and so each clinician's approach will be affected by their personal, clinical experience and expertise, and guided by their patients' expectations and circumstances.

Awareness and practice concerning oral cancer among Ayurveda and Homeopathy practitioners in Davangere District: A speciality-wise analysis.

CONTEXT: In India, oral cancer accounts for one-third of all cancers. Early detection and immediate intervention can lead to marked reduction in the morbidity and mortality. In India, Ayurveda and homeopathy practitioners are distributed widely in rural and urban areas and are easily accessible. Until date, no assessment on their oral cancer knowledge and practice has been done. AIMS: The present study was undertaken to evaluate the knowledge, awareness, and practice concerning oral cancer. SUBJECTS AND METHODS: Questionnaire comprising 15 questions was distributed to 42 Ayurveda and 38 homeopathy doctors in Davangere District, Karnataka, India, assessing their oral examination habits, knowledge on the risk factors, patient education, clinical signs of the disease and its treatment. STATISTICAL ANALYSIS USED: The results were analyzed using Chi-square test. RESULTS: Lesser number of the practitioners routinely examined oral mucosa (16.7% and 5.3%, respectively). Fewer advised their patients about the risk factors (2.4% and 2.6%). Less positive response was obtained for the correct method for confirmation of diagnosis (28.6% and 15.8%). Many doctors agreed that they had not undergone training in cancer institute (P = 0.29). Twenty-three (54.8%) Ayurveda and 28 (73.7%) homeopathy doctors opined that they did not have sufficient knowledge regarding early detection and prevention of oral cancer and many were desirous of receiving further information (97.6% and 84.2% respectively). CONCLUSIONS: This study attempts to highlight the need for improving the oral cancer knowledge and awareness among practicing Ayurveda and homeopathy doctors.

Chitosan based grey wastewater treatment--a statistical design approach.

In this present study, grey wastewater was treated under different operating conditions such as agitation time (1-3 min), pH (2.5-5.5), chitosan dose (0.3-0.6g/l) and settling time (10-20 min) using response surface methodology (RSM). Four factors with three levels Box-Behnken response surface design (BBD) were employed to optimize and investigate the effect of process variables on the responses such as turbidity, BOD and COD removal. The results were analyzed by Pareto analysis of variance (ANOVA) and second order polynomial models were developed in order to predict the responses. Under the optimum conditions, experimental values such as turbidity (96%), BOD (91%) and COD (73%) removals are closely agreed with predicted values.

Modeling and analysis of film composition on mechanical properties of maize starch based edible films.

The present study investigates the influence of composition (content of maize starch (1-3 g), sorbitol (0.5-1.0 ml), agar (0.5-1.0 g) and tween-80 (0.1-0.5 ml)) on the mechanical properties (tensile strength, elongation, Young's modulus, puncture force and puncture deformation) of the maize starch based edible films using four factors with three level Box-Behnken design. The edible films were obtained by casting method. The results showed that, tween-80 increases the permeation of sorbitol in to the polymer matrix. Increasing concentration of sorbitol (hydrophilic nature and plasticizing effect of sorbitol) decreases the tensile strength, Young's modulus and puncture force of the films. The results were analyzed by Pareto analysis of variance (ANOVA) and second order polynomial models were obtained for all responses with high R(2) values (R(2)>0.95). 3D response surface plots were constructed to study the relationship between process variables and the responses.

Molecular characterization and expression profile of ghrelin gene during different reproductive phases in buffalo (Bubalus bubalis).

Ghrelin, a novel motilin-related endogenous ligand for growth hormone secretagouge receptor, is implicated in various biological functions, including regulation of female reproduction. But the presence of ghrelin and its role in reproductive functions in buffalo, a species with poor reproductive efficiency, is not known. In the present study full-length ghrelin cDNA was isolated from bubaline abomasum, which encodes the entire prepropeptide of 116 amino acids. The deduced amino acid sequence of ghrelin of buffalo showed >95% and 31% identity with that of ruminants (cattle, sheep, and goat) and humans, respectively. Analysis of synonymous and nonsynonymous nucleotide substitutions in the coding region of ghrelin indicated that these sequences of different species have been under purifying selection. The 3995-bp amplicon of ghrelin gene consisting of 4 exons and 3 introns was cloned with genomic DNA from buffalo. Further, ghrelin expression was determined by quantitative real-time PCR, in situ hybridization, and immunohistochemistry in bubaline endometrial tissues at different stages of the estrous cycle and early pregnancy. Our results indicated the persistent expression of ghrelin mRNA and protein in the endometrium during stage I (day 3-5), stage II (day 6-15), and stage III (day 16-21) of the estrous cycle and also during early (~day 30-40) pregnancy. Immunohistochemistry and quantitative real-time PCR experiments indicated the relatively higher expression of ghrelin in the endometrium during stage II (day 6-15) of the estrous cycle and early pregnancy than during stage I (day 3-5) and stage III (day 16-21) of the estrous cycle, but no statistically significant difference in ghrelin expression was observed among stages. To conclude, the results of the present study indicate the persistent expression of ghrelin in the uterine endometrium throughout the estrous cycle and in early pregnancy which might be helpful in determining its role in buffalo reproduction.

Genomic analysis of between-cow variation in dermal fibroblast response to lipopolysaccharide.

The innate immune response plays a major role in defense against mastitis-causing pathogens. Identification of existing variation in innate immune signaling among cows and the underlying molecular causes for the variation may help in design of new mastitis control strategies. The dermal fibroblast has been used as a model cell type to explore between-cow variation in the ability of cells to produce IL-8 in response to lipopolysaccharide (LPS) treatment, and this response appears related to an animal's ability to respond to in vivo challenge with LPS or Escherichia coli mastitis. In this study, primary dermal fibroblast cultures of cows and microarray-based genomic analysis were used to investigate the cause(s) for the variable response to LPS. Fibroblast cultures from 2 cows, one with a low response phenotype (LR(array)) and another with a high response phenotype (HR(array)), were selected from our collection of fibroblast cultures established from 88 cows. The LR(array) fibroblast culture produced approximately 5-fold less IL-8 and IL-6 protein in response to 24-h LPS treatment than the HR(array) fibroblast culture. Genomic analysis of RNA obtained from 3 replicates of the 2 cultures before and after 8-h LPS treatment revealed a combined LPS-induced differential expression of 321 transcripts, indicating the robust response capability of the fibroblast cell. Under basal conditions, the microarray analysis revealed 2-fold less expression of toll-like receptor 4 (TLR4) in the LR(array) fibroblasts compared with the HR(array) fibroblasts, and this was associated with a marked reduction in expression of genes regulated by the TLR4-MyD88-dependent and TLR4-TRIF-dependent pathways (IL-8, IL-6, SAA3, CCL20, MX1, IRF1, and ISG20). The between-culture differential expression of TLR4 was confirmed and extended by quantitative PCR analysis (QPCR) that revealed a 33-fold lower expression of TLR4 in the LR(array) fibroblast culture. After LPS treatment, the difference in TLR4 expression increased to almost 50-fold and was associated with more than 8-fold lower expression of IL-8 and IL-6. No DNA sequence variations were identified in the proximal 1,300-bp promoter region of the TLR4 gene, and microarray analysis did not reveal a molecular explanation for the reduced TLR4 expression under either basal conditions or following exposure to LPS. The attenuated innate immune response of the LR(array) fibroblast culture to LPS may be caused by reduced TLR4 receptor expression. Also, the primary dermal fibroblast cells can be used to examine underlying causes for between-cow variations in key immune response pathways.

Between-cow variation in dermal fibroblast response to lipopolysaccharide reflected in resolution of inflammation during Escherichia coli mastitis.

Effective response to mammary gland infection depends on efficient early innate immune response. The desired response would be one that is sufficient to clear the infection with a rapid return to the production of high-quality milk and limited tissue damage. In this study, 43 early lactation cows were ranked based on the ability of their fibroblasts to produce IL-8 in response to Escherichia coli lipopolysaccharide. Subsequently, the effect of a low or high response phenotype on the response to E. coli mastitis was determined. Untreated fibroblasts produced no detectable IL-8, whereas the range of IL-8 production in response to LPS (100 ng/mL) was approximately 7-fold between the lowest and highest responding cultures. Similar patterns of between-cow variation were observed in fibroblast production of IL-8 and IL-6 in response to IL-1ß and Pam2CSK4 (a synthetic diacylated lipopeptide ligand). Four low and 4 high responder cows were challenged in late lactation with intramammary infusion of E. coli. All cows developed clinical mastitis in the challenged quarters and all cows cleared the infection within 8 d. However, somatic cell count began to decline earlier in the low responder group, and milk BSA concentration (an indicator of tissue damage) was also lower in low responders compared with high responders. Milk production from the challenged quarter was markedly depressed in both groups, but returned toward prechallenge values earlier in low responder cows. Dermal fibroblast cells appear predictive of a cow's response to mastitis. In this study, the low responder phenotype was sufficient to contain an E. coli infection with a more rapid return to the production of high quality milk.

The use of dermal fibroblasts as a predictive tool of the toll-like receptor 4 response pathway and its development in Holstein heifers.

The innate immune system comprises the host's first line of defense against invading pathogens, and variation in the magnitude of this response between animals has been shown to affect susceptibility to mastitis. The toll-like receptor (TLR) family of proteins initiates the response to invading bacteria, specifically with TLR4 recognizing lipopolysaccharide (LPS) of gram-negative microbes. The underlying genetic variation in the TLR4 pathway leading to differential response is not well understood; therefore, the objective of this work was to determine the efficacy in which the response to LPS by dermal fibroblasts could be used to predict the actual systemic response of that animal to an intravenous endotoxin challenge. To accomplish this, dermal fibroblasts were isolated from 15 Holstein heifers at 5, 11, and 16 mo of age and exposed to either LPS or IL-1ß; then, the production of IL-8 in medium was quantified by ELISA. Animals were ranked based upon the magnitude of the fibroblast IL-8 response, and 8 heifers were selected [4 low responders (LR) and 4 high responders (HR)] for challenge with an intravenous bolus dose (0.5 µg/kg of body weight) of LPS. Overall, between-animal variation in fibroblast IL-8 production following LPS or IL-1ß was high, indicating appreciable differences in the TLR4 pathway of the animals. Ranking of the fibroblast responses was consistent across the 3 sampling times for each animal; however, the absolute response increased, and the age at which the fibroblasts were obtained was consistent with the potential for age-related changes in cell function to affect immune function processes. Following systemic LPS challenge, HR heifers had higher plasma concentrations of tumor necrosis factor-α and IL-8 than LR heifers. However, LR heifers had a stronger febrile response than HR heifers. The use of dermal fibroblasts under laboratory conditions appears to represent a practical model for predicting the innate immune response in vivo and could act as an important tool in mapping genetic differences of the TLR4 pathway.

Comparative antimicrobial activity of callus and natural plant extracts of Solanum trilobatum L.

Comparison of natural plant and callus extracts of Solanum trilobatum L. was studied against two bacteria and fungi, for their antimicrobial activity using cup diffusion method. Various solvents such as chloroform, petroleum ether and ethanol were used. The leaf and stem segments of the plant were culturedon Murashige and S koog basal medium supplemented with various growth regulators. Maximum callus was recorded on medium containing 0.5 mg/lNAA and 0.5 mgj IKinetin. The results reveals that the stem and leaf callus extracts has shown significant activity against the tested microorganisms than the natural sample.

The wisdom behind third molar extractions.

The literature pertaining to the extraction of third molars is extensive. There is a large individual variation and a multitude of practitioners' beliefs and biases relating to the extraction of especially asymptomatic and pathology free third molars. With the current emphasis in dentistry being placed on clinicians to make evidence-based decisions, the routine removal of third molars has been re-assessed and questioned. The purpose of this paper was to evaluate past and present knowledge of third molar extractions and relate it to logical considerations relevant to science and the evidence-based decision-making process. This paper endeavours to encourage and stimulate clinicians to re-evaluate their views on third molar extractions based on suggested guidelines and current evidence.

Is orthodontic treatment without premolar extractions always non-extraction treatment?

While it is common in contemporary orthodontic and orthopaedic treatment to commence treatment for many growing patients during the mixed-dentition, the creation of anterior space, often involving the attempted distalization or holding-back of the upper and lower permanent molar teeth has been shown to commonly result in posterior space deficiencies. Although the extractions of permanent premolar teeth may have been avoided, the developing second and third permanent molars are often affected, so that third molar impaction results in many cases. This is not to say that orthodontic treatment carried-out without premolar extractions is not ideal in many cases, but on the available evidence, so-called absolute 'non-extraction' protocols should be questioned, so that both the dental profession and the public at large are not misled.

Possible involvement of L-type voltage-gated calcium channels in release of dopamine in the striatum of irradiated rats.

The object of this study was to determine the effect of exposure to gamma radiation on potassium chloride (KCl)-stimulated release of dopamine (DA) in the striatum of the rat. In addition, the effect of some calcium channel blockers [nicardipine, a blocker of the L-type voltage-gated N-type VGCC; Omega-agatoxin TK, a selective blocker of P-type VGCC; and nickel chloride (NiCl(2)), which preferentially blocks the T-type VGCC] on KCl-stimulated release of DA in the striatum in sham-irradiated and irradiated rats was determined. Exposure of rats to 1-10 Gy (60)Co gamma rays had no significant effect on KCl-stimulated release of DA in the striatum in comparison to sham-irradiated animals. Administering 100, 300 and 500 nM of Omega-agatoxin TK or 50, 100 and 200 nM of Omega-conotoxin GVIA significantly decreased the release of DA stimulated by KCl in both irradiated and sham-irradiated animals in a dose-dependent manner. However, 10, 30 and 50 microM of nicardipine decreased the release of DA in irradiated animals but not in sham-irradiated animals. It is unknown why doses of 5-20 microM NiCl(2) had no effect on the release of DA in sham-irradiated and irradiated animals. The results demonstrate that the doses of radiation used in this study had no effect on release of DA in the striatum. Multiple calcium channel types coexist to regulate release of DA. P- and N-type VGCCs are involved in release of DA in sham-irradiated and irradiated animals, whereas only L-type VGCCs are involved in release of DA in irradiated animals.

Effect of ionizing radiation on the release of cholecystokinin in the hypothalamus of the rat.

This study was designed to identify the mechanisms underlying the reduction in food intake in rats. Measurements were made of the release of cholecystokinin (CCK) stimulated by potassium chloride in the hypothalamus after (a) gamma irradiation (60Co), (b) treatment with the CCK-A and CCK-B antagonists L-364,718 and L-365,260 with and without radiation, (c) bilateral abdominal vagotomy, and (d) vagotomy with and without radiation and with and without L-364,718. The concentrations of CCK in hypothalamus perfusate were measured by a radioimmunoassay. Exposure of rats to 1, 3, 5 and 10 Gy (1 Gy/min) increased release of CCK in the hypothalamus in a manner that was dependent on dose. A dose of 5 Gy was chosen for further studies. Intraperitoneal (i.p.) administration of 10, 20 and 50 microg/kg of L-364,718 did not induce significant changes in release of CCK in sham-irradiated animals. However, the drug decreased the release of CCK induced by radiation in a dose-dependent manner. In contrast to L-364,718, 20-50 microg/kg of L-365,260 decreased the release of CCK in the hypothalamus in sham-irradiated animals but did not decrease release of CCK induced by exposure to radiation. Vagotomy produced an insignificant reduction in release of CCK compared to that in sham-irradiated controls. However, vagotomy decreased release of CCK in irradiated rats compared to the irradiated rats without vagotomy. Vagotomy and i.p. administration of 10, 20 and 50 microg/kg of L-364,718 decreased release of CCK in irradiated rats compared to that in irradiated rats without vagotomy. However, i.p. administration of 10, 20 and 50 microg/kg of L-364,718 did not induce significant decreases in release of CCK in the hypothalamus of vagotomized and irradiated animals compared to those in rats that were vagotomized and irradiated but not treated with L-364,718. These results demonstrate that radiation increases the release of CCK in the hypothalamus, and that this effect is inhibited by vagotomy and the administration of a CCK-A receptor antagonist. A CCK-A receptor antagonist may be used to mitigate a radiation-induced deficit in food intake.

Effect of Bay K 8644, calcimycin and phorbol ester on radiation-induced decreases in the release of norepinephrine in the hippocampus in rats.

Gamma radiation (10 Gy at 10 Gy/min from a 60Co source) induces a decrease in the release of norepinephrine in the hippocampus 48 h after exposure. The purpose of this study was to determine the effect of Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-2(trifluoromethylphenyl)py rid ine-5-carboxylate], an agonist for L- and N-type calcium channel subtypes; calcimycin [6S-[6alpha(2S*,3S*),8beta(R*),9beta,11alpha]-5( methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2(1H-pyrrol-2-yl)eth yl]-1,7-dioxaspiro[5,5]undec-2-yl]methyl]-4-benzoxazoleca rboxylic acid], a calcium ionophore which increases intracellular Ca2+; and phorbol 12-O-tetradecanoate 13-acetate (TPA), which stimulates protein kinase C (PKC) alone or in combination with decreases in the release of norepinephrine in the hippocampus 48 h after irradiation. Neither Bay K 8644 (1-100 nM), calcimycin nor TPA prevented the radiation-induced decreases in the release of norepinephrine in the hippocampus. However, 10 nM of Bay K 8644 or calcimycin in combination with 1-100 nM of TPA or 10 nM of TPA in combination with 1-100 nM of Bay K 8644 or calcimycin did prevent the radiation-induced decreases in the release of norepinephrine. These results suggest that stimulation of PKC by TPA and mobilization of calcium by Bay K 8644 or calcimycin are necessary to prevent the radiation-induced decreases in the release of norepinephrine in the hippocampus.