The Loss of α- and ß-Tubulin Proteins Are a Pathological Hallmark of Chronic Alcohol Consumption and Natural Brain Ageing.

Repetitive excessive alcohol intoxication leads to neuronal damage and brain shrinkage. We examined cytoskeletal protein expression in human post-mortem tissue from Brodmann's area 9 of the prefrontal cortex (PFC). Brain samples from 44 individuals were divided into equal groups of 11 control, 11 alcoholic, 11 non-alcoholic suicides, and 11 suicide alcoholics matched for age, sex, and post-mortem delay. Tissue from alcoholic cohorts displayed significantly reduced expression of α- and ß-tubulins, and increased levels of acetylated α-tubulin. Protein levels of histone deacetylase-6 (HDAC6), and the microtubule-associated proteins MAP-2 and MAP-tau were reduced in alcoholic cohorts, although for MAPs this was not significant. Tubulin gene expressions increased in alcoholic cohorts but not significantly. Brains from rats administered alcohol for 4 weeks also displayed significantly reduced tubulin protein levels and increased α-tubulin acetylation. PFC tissue from control subjects had reduced tubulin protein expression that was most notable from the sixth to the eighth decade of life. Collectively, loss of neuronal tubulin proteins are a hallmark of both chronic alcohol consumption and natural brain ageing. The reduction of cytosolic tubulin proteins could contribute to the brain volumetric losses reported for alcoholic patients and the elderly.

Hepatoprotective and antioxidant activities of Spondias mombin leaf and stem extracts against carbon tetrachloride-induced hepatotoxicity.

OBJECTIVE: Spondias mombin L. is a tree used in folk medicine in Nigeria for the treatment of hepatitis. This study was carried out to comparatively evaluate the hepatoprotective and antioxidant effects of S. mombin leaf and stem (SML and SMS) methanolic extracts in a rat model of carbon tetrachloride (CCl4)-induced hepatotoxicity. METHODS: Forty-two rats were distributed into seven groups. Groups A and B received water; groups C and D received 500 and 1000 mg/kg SML extract, respectively; groups E and F received 500 and 1000 mg/kg SMS extract, respectively; and group G received 100 mg/kg silymarin. Water, the two extracts, and silymarin were administered daily by oral gavage for 7 days. Hepatotoxicity was induced in groups B to G by the administration of CCl4 once on the seventh day. After 48 h, rats were sacrificed, and tissues and serum samples were examined for histological and biochemical indices of hepatotoxicity. RESULTS: Administration of CCl4 resulted in liver injury with significant elevation in the hepatocellular injury markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and conjugated bilirubin (CBIL), associated with a significant reduction in total circulatory protein. Pretreatment with SML and SMS extracts at both doses significantly ameliorated liver injury; lowered ALT, AST, ALP, TBIL, and CBIL levels; elevated cellular glutathione levels as well as catalase and superoxide dismutase activities; and decreased the levels of thiobarbituric acid reactive substances. CONCLUSION: This study provides preliminary evidence supporting the potential therapeutic benefit of S. mombin in xenobiotic-induced hepatotoxicity.

Hepatoprotective effect of hydromethanolic leaf extract of Musanga cecropioides (Urticaceae) on carbon tetrachloride-induced liver injury and oxidative stress.

OBJECTIVE: Natural antioxidant products are gaining popularity as treatments for various pathological liver injuries. Musanga cecropioides (Urticaceae) leaf extract is used in ethnomedicine for the management of jaundice and other hepatic ailments in Ibibio, Nigeria. This study evaluated the hepatoprotective and antioxidant effects of M. cecropioides hydromethanolic leaf (MCHL) extract against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. METHODS: Liver damage was induced by administering CCl4 dissolved in liquid paraffin (2 mL/kg bw 1:1 intraperitoneally) after pretreatment with MCHL extract for 7 days. Thereafter, acute hepatotoxicity was evaluated in 36 Wistar rats divided into six groups (A-F) of six animals each. Group A served as the negative control; B received CCl4 1 mL/kg only; C-E received 70.7, 141.4, and 282.8 mg/kg MCHL extract, respectively; and F received silymarin 100 mg/kg daily for 7 days by oral gavage. After 48 h, the rats were sacrificed, and samples obtained from them were assayed for histological and biochemical biomarkers of hepatotoxicity. RESULTS: The MCHL extracts significantly (p < 0.001-0.05) reduced the increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), conjugated bilirubin (CBIL), and total bilirubin (TBIL) levels induced by CCl4 intoxication. There was no significant alteration in haematological indices or weight following administration of the MCHL extracts. Histopathological examinations revealed mitotic bodies in the 141.4 mg/kg MCHL extract-treated rats, an indication of tissue repair processes. CONCLUSION: The MCHL extract has a dose-specific hepatoprotective effect; hence, the utilisation of this extract for the management of hepatitis requires caution.

Antimicrobial activity of Carpolobia lutea extracts and fractions.

Carpolobia lutea (G. Don) (Polygalaceae) is a tropical medicinal plant putative in traditional medicines against gonorrhea, gingivitis, infertility, antiulcer and malaria. The present study evaluated the antimicrobial, antifungal and antihelicobacter effects of extracts C. lutea leaf, stem and root. The extracts were examined using the disc-diffusion and Microplates of 96 wells containing Muller-Hinton methods against some bacterial strains: Eschericia coli (ATCC 25922), E. coli (ATCC10418), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), Staphyllococus aureus (ATCC 6571), Enterococcus faecalis (ATCC 29212) and Bacillus subtilis (NCTC 8853) and four clinical isolates: one fungi (Candida albican) and three bacteria (Salmonella, Sheigella and staphylococcus aureus). The Gram-positive bacteria: Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 19659) and the Gram-negative bacteria: Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Cândida albicans (ATCC 18804) and Helicobacter pylori (ATCC 43504). Some of these extracts were found to be active against some tested strains but activity against H. pylori was >1000mg/ml and good fungistatic activity against C. albican. The MIC against C. albican is in the order n-HF > CHF > ETF= EAF.The order of potency of fraction was the ethanol root > n-HF leaf > ethanol fraction stem > chloroform fraction leaf = ethyl acetate fraction leaf. Polyphenols were demonstrated in ethanol fraction, ethyl acetate fraction, crude ethyl acetate extract and ethanol extract, respectively. These polyphenols isolated may partly explain and support the use of C. lutea for the treatment of infectious diseases in traditional Ibibio medicine of Nigeria.

Patient-reported outcomes of therapy with two brands of ibuprofen

Objective: To investigate patients’ reported outcome following medication with two brands of 400 mg ibuprofen used to alleviate musculoskeletal pains. Methods: Adult peasant manual laborers (85) who met criteria were randomly assigned to receive either of the brands (A or B). Data on pain alleviation were gathered using the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analogue Scale (VAS), Present Pain Intensity (PPI), and Clinical Global Impression of Improvement (CGII) scales. Interval data obtained from the two brands were compared using the Students’ t-test at 95% confidence interval. Results: There were 42 participants, mean age=29.2 (SD=1.37) assigned to brand A and 43 (mean age=28.8 SD=1.14) in brand B of ibuprofen 400 mg. Brand B was consistently rated higher than brand A. Scores for medication efficacy were 10.4 (SD=1.65) (brand A) and 11.4 (SD=1.68) (brand B); t=2.768, P=0.007. Alleviation of pain symptoms: 10.8 (SD=1.64) and 11.6 (SD=1.72); t = 2.194, P=0.031. Similarly, rated scores on the impact of pain on quality of life were 10.5 (SD=2.00) and 12.1 (SD=1.85); t=3.830, P<0.001. There was a reduction in Present Pain Intensity scores by 32.7% and 34.3% for Brand A and brand B participants respectively. The decrease in Visual Analog pain scale score was 35.9% and 37.3% for brand A and brand B participants respectively. The decrease in SF-MPQ was by 85.1% and 69.9% for the brand A and brand B groups respectively. The clinical global impression of improvement for both groups of patients indicated an improvement rate of 71.4% and 61.9% for brand A and 81.4% and 74.4% for brand B participants. Conclusion: This clinical study infers that though the two brands of ibuprofen 400 mg are legally pharmaceutical equivalent, they are not clinically equivalent. In most of the parameters evaluated, brand B was rated more efficacious than brand A. This explains the patients’ preferences and demand for this brand of ibuprofen in the Nigerian community (AU)

Objetivo: Investigar los resultados comunicados por los pacientes después de la medicación con dos marcas de 400 mg de ibuprofeno usados para aliviar dolor musculo-esquelético. Métodos: Se asignó aleatoriamente a adultos trabajadores manuales del campo para recibir una de dos marcas (A o B). Se recogieron datos del alivio del dolor usando las escalas Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analogue Scale (VAS), Present Pain Intensity (PPI), and Clinical Global Impression of Improvement (CGII). Los datos obtenidos con las dos marcas se compararon usando es test t de Student en un intervalo de confianza del 95%. Resultados: Hubo 42 participantes de edad media=29,2 (DE=1,37) asignados a la marca A y 43 (edad media=28,8 DE=1,14) a la marca B de ibuprofeno 400 mg. La marca B fue evaluada consistentemente más alto que la A. Las puntuaciones de eficacia fueron 10,4 (DE=1,65) marca A y 11,4 (DE=1,68) marca B; t=2,768, P=0,007. El alivio del dolor: 10,8 (DE=1,64) and 11,6 (DE=1,72); t = 2,194, P=0,031. Del mismo modo, las puntuaciones del impacto del dolor en la calidad de vida fueron 10.5 (DE=2,00) y 12.1 (DE=1,85); t=3,830, P<0,001. Hubo una reducción en las puntuaciones en el Present Pain Intensity del 32,7% y 34,3% para los participantes de las marcas A y B respectivamente. La disminución en la Escala Visual Analógica del dolor fue del 39,5% y 37,7% para las marcas A y B respectivamente. La disminución en el SF-MPQ fue del 85,1% y 69,9% para las marcas A y B respectivamente. La impresión clínica global de mejoría para ambos grupos de pacientes indicó una tasa de mejoría de 71,4% y 61,9% para la marca A y de 81,4% y 74,4% para la marca B. Conclusión: Este estudio clínico infiere que las dos marcas de ibuprofeno 400 mg son legalmente equivalentes farmacéuticas, y que no son clínicamente equivalentes. En la mayoría de los parámetros evaluados, la marca B fue valorada más eficaz que la marca A. Esto explica las preferencias de los pacientes y la solicitud de esta marca de ibuprofeno en la comunidad nigeriana (AU)

Patient-reported outcomes of therapy with two brands of ibuprofen.

OBJECTIVE: To investigate patients' reported outcome following medication with two brands of 400 mg ibuprofen used to alleviate musculoskeletal pains. METHODS: Adult peasant manual laborers (85) who met criteria were randomly assigned to receive either of the brands (A or B). Data on pain alleviation were gathered using the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analogue Scale (VAS), Present Pain Intensity (PPI), and Clinical Global Impression of Improvement (CGII) scales. Interval data obtained from the two brands were compared using the Students' t-test at 95% confidence interval. RESULTS: There were 42 participants, mean age=29.2 (SD=1.37) assigned to brand A and 43 (mean age=28.8 SD=1.14) in brand B of ibuprofen 400 mg. Brand B was consistently rated higher than brand A. Scores for medication efficacy were 10.4 (SD=1.65) (brand A) and 11.4 (SD=1.68) (brand B); t=2.768, P=0.007. Alleviation of pain symptoms: 10.8 (SD=1.64) and 11.6 (SD=1.72); t = 2.194, P=0.031. Similarly, rated scores on the impact of pain on quality of life were 10.5 (SD=2.00) and 12.1 (SD=1.85); t=3.830, P<0.001. There was a reduction in Present Pain Intensity scores by 32.7% and 34.3% for Brand A and brand B participants respectively. The decrease in Visual Analog pain scale score was 35.9% and 37.3% for brand A and brand B participants respectively. The decrease in SF-MPQ was by 85.1% and 69.9% for the brand A and brand B groups respectively. The clinical global impression of improvement for both groups of patients indicated an improvement rate of 71.4% and 61.9% for brand A and 81.4% and 74.4% for brand B participants. CONCLUSION: This clinical study infers that though the two brands of ibuprofen 400 mg are legally pharmaceutical equivalent, they are not clinically equivalent. In most of the parameters evaluated, brand B was rated more efficacious than brand A. This explains the patients' preferences and demand for this brand of ibuprofen in the Nigerian community.