Tuberculosis, diabetes and epilepsy are the diseases requiring prolonged treatment by certain drugs. Unfortunately their toxic effects sometimes decline the standards of life of the patients in terms of physical and psychological well being. Hepatic toxicity of rifampin, phenytoin, sulfonylureas and carbamazepine cannot be neglected in this regard. These drugs may reduce the efficiency of liver to a large extent. Therefore it is important to consider an adjuvant for this purpose as these drugs cannot be compromised in term of doses, dosage forms or responses. The study has been planned to see the beneficial role of altering liver blood flow in reducing the toxicity of drugs. Propranolol is a non selective beta adrenergic receptor antagonist which reduces the hepatic blood flow. It is scientific to believe that it can reduce the amount of hepatotoxic drug in liver by reducing the hepatic blood flow thereby reducing the DILI. The hepatotoxicity of these drugs with or without propranolol in term of anatomical changes, enzymatic assay, qualitative and quantitative histopathological studies and electron microscopy were evaluated. In this study significant number of healthy rabbits were used which will be divided into nine different groups from A to H. Calculated dose of all four drugs were given to the assigned groups of rabbits with or without propranolol as per dosing schedule. Group A was considered as control and received distilled water only while group B and C were received CBZ alone and in combination of propranolol, respectively. Liver function test and histological evaluation by H and E staining and scanning electron microscopy (SEM) were carried at the end of dosing by using standard procedures. Serum level of ALT, ALP, γGT and bilirubin were significantly (p<0.05) increased in CBZ treated group as compared to control while not significantly elevated in CBZ plus propranolol treated groups. But significant reduction in hepatic parameters was seen in CBZ plus propranolol vi group as compared to CBZ alone. The histopathological examination revealed various features of hepatic architecture damage in CBZ treated group. These results were also supported by micrometry and SEM. The hepatic damage induced by CBZ was successfully ameliorated by propranolol. The hepatic architecture was effectively recovered in propranolol and CBZ treated group which showed in Hand E staining and SEM. Group D and E received rifampicin (RIF) alone and in combination of propranolol respectively. Similar parameters were used to explore the hepatoxic effects of RIF and protection was given by propranolol. Results of liver function test revealed that RIF significantly elevate the serum levels of ALT, ALP, γGT and bilirubin as compared to control. These levels were also higher in RIF plus propranolol treated group but when comparing the levels in between group D and E it was illustrated that propranolol provide significant protection to the RIF induced damage. Histology and SEM of liver sections also supported these results. Liver damage induced by RIF expressed as central vein dilation, infiltration of inflammatory cells, portal vein dilation and damage of hepatocytes. Micrometry revealed that number of viable hepatocytes, their diameter and nuclear diameter were altered.SEM micrograph showed distorted and swollen hepatic cords. All of these changes successfully turned to normal by combined administration of propranolol. propranolol successfully improve the hepatic architecture proved by both qualitative and quantitative microscopy. Glibenclamide (GLB) alone or in combination of propraranolol was administered in Group F and G respectively. Serum levels of ALT, ALP, γGT and bilirubin were estimated and compared in both groups. Results showed that GLB caused significant elevation of liver functions as compared to control. There values of ALT and ALP were significantly high in vii group G as compare to control.When comparing these levels between group G and F significant elevations were seen in group F which showed that propranolol reduced the level of serum ALT, ALP, γGT and bilirubin when administered with GLB. The granuloma and necrosis seen in GLB treated liver was not seen in group G rabbit’s liver. The number of viable hepatocytes and their nuclear diameter which were considerably reduced by GLB were effectively preserved to normal after administering propranolol as adjuvant. Thus histological evaluation of liver tissue through H and E staining and SEM showed that combined administration of GLB and propranolol is helpful in reducing the GLB induced liver damage. Group H and I received phenytoin (PHT) alone and in combination with propranolol, respectively. Evaluation of hepatic functions test expressed that the serum levels of ALT, ALP, γGT and bilirubin were significantly raised in PHT treated group. Serum levels of ALT, ALP, γGT and bilirubin were also significantly high in PHT and propranolol treated group as compared to control. When comparing the values between these two groups it was illustrated that propranolol offered significant protection to the liver. Histological examination of Hand E stained liver tissue showed that PHT caused severe hepatic damage expressed as necrosis, hemorrhage and dilation of sinusoids, inflammation and dilation and congestion of portal vein. Combined administration of propranolol and PHT reduced these changes induced by PHT alone. The micrometric estimation of H and E stained section of live supported the above mentioned results.Minor inflammatory cells were seen and necrosis is absent in liver section of group I rabbits. SEM of liver of group H also showed damage and ruptured hepatic cords with cellular swelling. Protection provided by viii propranolol also expressed through this technique. Propranolol improved the hepatic architecture clearly seen in the SEM micrograph of group I rabbit. It is summarized that all of the aforementioned drugs produced threatened effect on the liver. Propranolol is an approved treatment of portal hypertension and esophageal varices in cirrhotic patient. This effect of propranolol is due to reduction in hepatic blood flow. Propranolol offered beneficial effect in drug induced hepatoxicity may be due to its diminution of portal blood flow thus reducing the supply of noxious substance to the liver. Propranolol may also ameliorate drug induced liver disease due to its affect on cytochrome P450 or due to owing antioxidant action.
Background of the study: Tibia Vara is defined as a growth abnormality which leads to Varus malalignment of the lower limb. It is caused by excessive loading on the medial part of proximal tibia. Progressive Tibia Vara can result in a bowleg deformity which is most noticeable in posteromedial part of upper tibial physis. Other than that, it gives rise to in toeing of feet and lateral knee thrust, altering the normal biomechanics of an individual. This study aim to determine the frequency of Tibia Vara among obese adolescents (13-18years).
Methodology: A descriptive cross-sectional study was done using non probability convenient sampling. Total 214 obese adolescents of age range 13 to 18 years were recruited from different parks and schools of Lahore. Adolescents with BMI less than 30 and with history of fracture or dislocation in the lower limb were excluded from the study. Manual goniometer was used to assess tibia vara in obese adolescent which had an intra-rater reliability of 0.75.
Results: Out of 214 obese adolescents, 128 were male and 86 were female. The percentage of Tibia Vara in this population was found to be 38% (n= 82). Whereas; on the basis of gender, male participants presenting with Tibia vara was found to be 26% (n= 56) and the percentage of females reported with Tibia vara was only 12% (n= 26).
Conclusion: Tibia vara had been reported in 38% of the obese adolescents in Lahore, Pakistan. Whereas, on the basis of gender most frequently tibia vara was reported among male participants.
Salmonella enterica is a Gram-negative facultative anaerobic bacteria. It belongs to the family of Enterobacteriaceae. Infections caused by Salmonella species are major threat to the human and animal health. After 1-3 days of ingestion of contaminated food, the patient develops diarrhea, fever, vomiting, and abdominal cramps. The situation is exacerbated if not treated promptly. Whole genome sequencing projects of clinically significant serovars of S. enterica have opened new perspectives of medical research. Using the genomic data, novel approaches are being employed throughout the world to find new protein targets for drug designing and screening. Targeting the essential metabolic pathways of the bacteria is the approach which we have focused in our study. The protein sequence and metabolic pathway data of the core proteome of S. enterica was analyzed in comparison to that of Homo sapiens. Various computational tools (BLASTp, CD-HIT, and Shell scripting) and datasets (NCBI, DEG, and KEGG) were extensively utilized to find non-homologous and essential enzymes of the pathogen. We discovered 73 enzymes belonging to metabolic pathways found only in the bacteria but not in H. sapiens, and proposed them as potential drug targets. Later, we selected an essential outer membrane protein complex (LptD/E) of S. enterica involved in lipopolysaccharide assembly, as a target in search of an inhibitor of the PPI complex. Druggable sites at the interface of PPI were identified by PocketQuery followed by virtual screening of the ZINC database of commercially available compounds using the ZINCPharmer tool. Energy minimization and scoring of short-listed compounds was performed using SMINA. A rational screening of >10,000 compounds resulted in 3 compounds depicting favorable polar interactions and optimal conformation for binding with the LptD protein. We propose that this interaction may lead to block the LptD interaction with LptE and lipid molecules and in result may block the LPS assembly.