Spectrophotometric Analysis of Oxytetracycline Brands Available Over-the-Counter for Veterinary Use in South Western Nigeria

Chemotherapy with oxytetracycline in livestock is reportedly faced withincreasing therapeutic failure and resistant bacteria strains circulating inhumans, animals and the environment. This study determined the actualconcentrations in some dosage forms of oxytetracycline available in Southwest Nigeria labelled for veterinary use by spectrophotometric method of analysis. Eight 5% (50mg/ml) and four 20% (200mg/ml) preparations of injectable oxytetracycline were purchased from veterinary pharmacies in Ibadan. The mean concentration of oxytetracycline obtained from formulations ranged between 0.484mg/ml and 0.757 mg/ml. Al l the commercial formulat ions contained less than the label led concentration when 1mg/ml of these samples was compared with 1mg/ml of theanalytical grade of oxytetracycline. Therapy failures and development ofbacterial resistance to oxytetracycline could therefore result from proliferation of fake or sub- s tandard drugs and indiscriminate use or abuse. There is need for strict regulation and quality control of importation, marketing and use of veterinary drugs in Nigeria. Also, there is need for pharmaco-vigilance a n d p h a rma c o - e p i d emi o l o g i c a l investigation of chemotherapeutic agents,which is recommended to ensure their efficacy for animal health and food safety

Studies on the anti-inflammatory, analgesic and antipyrexic activities of betulinic acid derived from Tetracera Potatoria.

Background: The anti-inflammatory and anti-nociceptive activity of betulinic acid (BA) was investigated in this study. The triterpene was isolated from the ethyl acetate extract of Tetracera potatoria and its structure was verified by IR and NMR spectroscopy. The bioactivity of this compound was assessed using carrageenan-induced paw oedema in rats and carrageenan-induced pulmonary oedema in mice for the antiinflammatory activity, while acetic acid-induced writhing test in mice and zymosan-induced fever in rats were used for analgesic test.Materials and Methods: Rats and mice were randomly divided into groups of five animals. For each experiment, betulinic acid at 10, 20 or 40mg/kg b.w was administered intraperitoneally to the first three groups respectively. The fourth group was administered with indomethacin (10mg/kg) or acetylsalicylic acid (150mg/kg), while the fifth group was administered with distilled water (10ml/kg). Data obtained were expressed as mean±S.E.M and significant differences were determined at p<0.05.Results: BA significantly reduced carrageenan-induced paw oedema by 11.0%, 45.7%, 68.6% or pulmonary oedema by 25.6, 29.2 and 45.13% dose dependently. 40 mg/kg of BA inhibited paw oedema by 68.6% comparably to acetylsalicylic acid (71.4%) or indomethacin (51.33%) respectively. Abdominal writhing was also significantly (p<0.05) reduced to 17.20 writhes by BA (40mg/kg) comparable to Indomethacin (16.3writhes). Fever was inhibited by BA most significantly by 3hours post-injection of zymosan (1.00, 1.45, 0.000C) and this inhibitory effect was higher than that observed for acetylsalicylic acid (0.300C).Conclusion: Betulinic acid derived from Tetracera potatoria exhibited potent anti-inflammatory, analgesic or antipyrexic activity which is comparable to indomethacin or acetylsalicyclic acid.Keywords: Anti-inflammatory, analgesia, antipyrexia, betulinic acid, Tetracera potatori

Effect of Sub-Chronic Administration of Tetracera potatoria Roots Extract and Betulinic Acid from the Plant on Haematology and Serum Biochemistry of Wistar Rats

Tetracera potatoria is used as natural remedy for a wide range of diseases in West Africa. Anti-ulcerogenic and anti inflammatory effects of T. potatoria are reported to be induced by Betulinic acid (BA). This study was aimed at assessment of the safety of T. potatoria and BA using acute and sub-chronic toxicity methods.Methanol extract of T. potatoria root (100, 500 and 1000 mg/kg) and BA (10, 20 and 40 mg/kg) isolated from the extract were administered to Wistar rats for 28 consecutive days in the subchronic toxicity study. Each experiment had control groups (n=5) which were administered with distilled water (10ml/kg). Whole blood and serum samples were collected from the rats for hematology and serum biochemistry on day 29.T. potatoria extract induced significant decreases in PCV from 42.8±1.5% (control) to 32.7±2.2% (1000mg/kg) 6 and RBC from 12.8±0.4 X10 /μl to 6 11.6±9.1X10 /μl, but increased WBC 3 levels from 7.8±2.3 X10 /μl (control) to 3 9.1±1.2 X10 /μl (500mg/kg). BA induced decreases in PCV from 42.8±1.2% to 41.8±0.4%, and RBC 6 from 12.7±7.6X10 /μl to 6.1±1.1 6 X10 /μl. Serum biochemistry showed significant increases in ALT from  48.5±2.2 U/L to 66.75±12.5 in rats administered with BA (40mg/kg), but relatively normal AST. Triglyceride levels were non-significantly reduced in T. potatoria treated rats but were increased from 74.0±3.8 mg/dl (control) to 139.3±4.8 mg/dl in rats administered with BA (40 mg/kg).In conclusion, sub-acute administration of T. potatoria root was relatively nontoxic, but BA showed relatively more toxicity to blood cells and a tendency to cause dyslipidemia.Keywords: Tetracera potatoria, Betulinic acid, haematology, serum biochemistr

Assessment of cardiotoxic potential of methanol extract of red cultivar Allium cepa

The effects of oral administration of crude methanol extract of red cultivar Allium cepa (Onion) on serum cardiac troponin (cTnI) in cardiac muscle and some haematological parameters were investigated in this study. Fifty five (55) male albino rats were housed and fed with standard growers ration and water ad libitum. There were three major groups; A, B and C containing twenty five (25), twenty five (25) and five (5) rats respectively. Group C was the control group while groups A and B were sub-divided into 5 groups of 5 rats each. Group A was administered with red cultivar A. cepa extract at doses of 100 mg/kg, 200 mg/kg, 400 mg/kg, 800 mg/kg and 1200 mg/kg for 14 days while group B rats were administered with the doses of red cultivar A. cepa for 28 days. Blood samples were collected from the retro-orbital sinus for haematology and cardiac troponin-I assay, histopathological examination of the heart was also done. Haematology showed significant (p<0.05) progressive decrease in packed cell volume (PCV), red blood cell (RBC) and haemoglobin (Hb) concentration and there was progressive elevation of mean corpuscular volume (MCV). Dose-independent elevation of serum cardiac troponin-I (cTnI) with varying degrees of myocardial injuries was observed. This study further postulates a correlation between the A. cepa-induced anaemia and increased cTnI which may be caused by myocardial ischaemia. In conclusion, this study reported the capability of red cultivar A. cepa to induce anaemia and cause myocardial injury as expressed with statistical significant (p<0.01) increase in serum cTnI. Medicinal use of red cultivar A. cepa is therefore recommended to be limited to lower doses and for short duration to prevent the haemotoxic and cardiotoxic potentials.Keywords: Allium cepa, Cardiac troponin-I, Cardiotoxicity, Haemotoxicity, Medicinal, Red cultiva

Somatic growth dynamics of West Atlantic hawksbill sea turtles: a spatio-temporal perspective

This is the final version of the article. Available from the publisher via the DOI in this record.Somatic growth dynamics are an integrated response to environmental conditions. Hawksbill sea turtles (Eretmochelys imbricata) are long-lived, major consumers in coral reef habitats that move over broad geographic areas (hundreds to thousands of kilometers). We evaluated spatio-temporal effects on hawksbill growth dynamics over a 33-yr period and 24 study sites throughout the West Atlantic and explored relationships between growth dynamics and climate indices. We compiled the largest ever data set on somatic growth rates for hawksbills – 3541 growth increments from 1980 to 2013. Using generalized additive mixed model analyses, we evaluated 10 covariates, including spatial and temporal variation, that could affect growth rates. Growth rates throughout the region responded similarly over space and time. The lack of a spatial effect or spatio-temporal interaction and the very strong temporal effect reveal that growth rates in West Atlantic hawksbills are likely driven by region-wide forces. Between 1997 and 2013, mean growth rates declined significantly and steadily by 18%. Regional climate indices have significant relationships with annual growth rates with 0- or 1-yr lags: positive with the Multivariate El Niño Southern Oscillation Index (correlation = 0.99) and negative with Caribbean sea surface temperature (correlation = −0.85). Declines in growth rates between 1997 and 2013 throughout the West Atlantic most likely resulted from warming waters through indirect negative effects on foraging resources of hawksbills. These climatic influences are complex. With increasing temperatures, trajectories of decline of coral cover and availability in reef habitats of major prey species of hawksbills are not parallel. Knowledge of how choice of foraging habitats, prey selection, and prey abundance are affected by warming water temperatures is needed to understand how climate change will affect productivity of consumers that live in association with coral reefs

Development of a TaqMan Allelic Discrimination Assay for detection of Single Nucleotides Polymorphisms associated with anti-malarial drug resistance

<p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance poses a threat to current global efforts towards control and elimination of malaria. Several methods are used in monitoring anti-malarial drug resistance. Molecular markers such as single nucleotide polymorphism (SNP) for example are increasingly being used to identify genetic mutations related to anti-malarial drug resistance. Several methods are currently being used in analysis of SNP associated with anti-malarial drug resistance and although each one of these methods has unique strengths and shortcoming, there is still need to improve and/or develop new methods that will close the gap found in the current methods.</p> <p>Methods</p> <p>TaqMan Allelic Discrimination assays for detection of SNPs associated with anti-malarial drug resistance were designed for analysis on Applied Biosystems PCR platform. These assays were designed by submitting SNP sequences associated with anti-malarial drug resistance to Applied Biosystems website. Eleven SNPs associated with resistance to anti-malarial drugs were selected and tested. The performance of each SNP assay was tested by creating plasmid DNAs carrying codons of interests and analysing them for analysis. To test the sensitivity and specificity of each SNP assay, 12 clinical samples were sequenced at codons of interest and used in the analysis. Plasmid DNAs were used to establish the Limit of Detection (LoD) for each assay.</p> <p>Results</p> <p>Data from genetic profiles of the <it>Plasmodium falciparum </it>laboratory strains and sequence data from 12 clinical samples was used as the reference method with which the performance of the SNP assays were compared to. The sensitivity and specificity of each SNP assay was establish at 100%. LoD for each assay was established at 2 GE, equivalent to less than 1 parasite/μL. SNP assays performed well in detecting mixed infection and analysis of clinical samples.</p> <p>Conclusion</p> <p>TaqMan Allelic Discrimination assay provides a good alternative tool in detection of SNPs associated with anti-malarial drug.</p

Long-Term Climate Forcing in Loggerhead Sea Turtle Nesting

The long-term variability of marine turtle populations remains poorly understood, limiting science and management. Here we use basin-scale climate indices and regional surface temperatures to estimate loggerhead sea turtle (Caretta caretta) nesting at a variety of spatial and temporal scales. Borrowing from fisheries research, our models investigate how oceanographic processes influence juvenile recruitment and regulate population dynamics. This novel approach finds local populations in the North Pacific and Northwest Atlantic are regionally synchronized and strongly correlated to ocean conditions—such that climate models alone explain up to 88% of the observed changes over the past several decades. In addition to its performance, climate-based modeling also provides mechanistic forecasts of historical and future population changes. Hindcasts in both regions indicate climatic conditions may have been a factor in recent declines, but future forecasts are mixed. Available climatic data suggests the Pacific population will be significantly reduced by 2040, but indicates the Atlantic population may increase substantially. These results do not exonerate anthropogenic impacts, but highlight the significance of bottom-up oceanographic processes to marine organisms. Future studies should consider environmental baselines in assessments of marine turtle population variability and persistence

GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats

BACKGROUND:By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans. METHODOLOGY:Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, alcohol preferring (P) and non-preferring (NP) rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was undertaken. PRINCIPAL FINDINGS:Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10⁻¹⁴, 7×10⁻¹¹ respectively). Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in NSF, implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with GPHN, encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (GAD1, GAD2), alcoholics (GABRA2) and P rats (ABAT, GABRG3). CONCLUSIONS/SIGNIFICANCE:Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications

Regulation of miR-146a by RelA/NFkB and p53 in STHdhQ111/HdhQ111 Cells, a Cell Model of Huntington's Disease

Huntington's disease (HD) is caused by the expansion of N-terminal polymorphic poly Q stretch of the protein huntingtin (HTT). Deregulated microRNAs and loss of function of transcription factors recruited to mutant HTT aggregates could cause characteristic transcriptional deregulation associated with HD. We observed earlier that expressions of miR-125b, miR-146a and miR-150 are decreased in STHdhQ111/HdhQ111 cells, a model for HD in comparison to those of wild type STHdhQ7/HdhQ7 cells. In the present manuscript, we show by luciferase reporter assays and real time PCR that decreased miR-146a expression in STHdhQ111/HdhQ111 cells is due to decreased expression and activity of p65 subunit of NFkB (RelA/NFkB). By reporter luciferase assay, RT-PCR and western blot analysis, we also show that both miR-150 and miR-125b target p53. This partially explains the up regulation of p53 observed in HD. Elevated p53 interacts with RelA/NFkB, reduces its expression and activity and decreases the expression of miR-146a, while knocking down p53 increases RelA/NFkB and miR-146a expressions. We also demonstrate that expression of p53 is increased and levels of RelA/NFkB, miR-146a, miR-150 and miR-125b are decreased in striatum of R6/2 mice, a mouse model of HD and in cell models of HD. In a cell model, this effect could be reversed by exogenous expression of chaperone like proteins HYPK and Hsp70. We conclude that (i) miR-125b and miR-150 target p53, which in turn regulates RelA/NFkB and miR-146a expressions; (ii) reduced miR-125b and miR-150 expressions, increased p53 level and decreased RelA/NFkB and miR-146a expressions originate from mutant HTT (iii) p53 directly or indirectly regulates the expression of miR-146a. Our observation of interplay between transcription factors and miRNAs using HD cell model provides an important platform upon which further work is to be done to establish if such regulation plays any role in HD pathogenesis

Genome-wide analyses reveal a potential role for the <em>MAPT</em>, <em>MOBP</em>, and <em>APOE </em>loci in sporadic frontotemporal dementia

\ua9 2024 The Author(s)Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 7 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 7 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 7 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex