Pain relief in neuropathic pain-a comparison between 0.5% bupivacaine and 0.5% bupivacaine streptomycin combination

Objective: To compare the effectiveness of a combination of streptomycin and bupivacaine for the management of neuropathic pain against bupivacaine alone

Study Design: A randomized controlled double blinded trial

Place and Duration of Study: Pain clinic Combined Military Hospital [CMH] Rawalpindi, CMH Nowshera, Dermatology Dept. Military Hospital [MH] Rawalpindi, Department of Medicine, Surgery CMH Nowshera Feb 2009 to Feb 2010

Material and Methods: Fifty patients with post herpetic neuralgia [PHN], 10 patients with trigeminal neuralgia and 20 patients with nerve entrapment pain were included in the study. For each type of neuropathic pain, the patients were randomly divided into two groups. Group [B] received nerve blocks using 0.5% bupivacaine and group [BS] received nerve blocks using 0.5% bupivacaine and streptomycin Igm combination. A series of four nerve blocks on alternate days were given. VAS [Visual Analogue Scale] was recorded at four, eight and twelve weeks after the last nerve block. Mean baseline VAS and at 12 weeks post treatment in groups B and BS were compared for pain relief and the mean VAS at 12 week post treatment in both the groups was compared for the difference in pain relief between the two groups. Students't test was used for statistical analysis utilizing SPSS 10 versions

Results: Post herpetic neuralgia - group [B]: at 12 weeks, mean VAS was 5.75 in gp [B] and 2.26 in gp [BS] respectively. Nerve entrapment pain- group [B] at 12 weeks, mean VAS was 6.62 whereas in group [BS] VAS was 1.33. Trigeminal neuralgia-group [B] At 12 weeks mean VAS was 7.0. gp [BS] mean VAS was 1. Pain relief achieved was excellent

Conclusion: Streptomycin and bupivacaine combination is an effective modality to manage neuropathic pain. The pain relief achieved by streptomycin-bupivacaine combination is superior to that achieved with bupivacaine alone

Personality traits of the adjusted and maladjusted medical students in punjab medical college, Faisalabad, Pakistan

Objective: The study was designed to examine the association between the personality traits and adjustment level of medical students

Method: 190 medical students from Punjab Medical College, Faisalabad participated in this study through purposive convenient sampling technique. Personality traits were measured through Gordon Personal Inventory [GPI] and Gordon Personal Profile [GPP], while adjustment and mal adjustment was assessed through Rotter's Incomplete Sentences Blanks [RISB]. The results were obtained through chi square statistics on SPSS version 17

Results: Results showed that out of 190 medical students 173 students [91%] were well adjusted. While 17 students [9%] obtained RISB scores above the cutoff point hence they were labeled as mal adjusted. Hypothesis testing with Chi square test has shown statistically significant differences in the scores on the trait of responsibility, cautiousness, personal relationship and vigor among adjusted and mal adjusted medical students. Mal adjusted students were seen associated with below average scores on all previously mentioned traits

Conclusion: The traits of responsibility, cautiousness, personal relationship and vigor are crucial for the adjustment in the society. So the parents and teachers should play their part in improving the fabric of the society by the means of building and emphasizing upon the sense of responsibility, cautious behavior, balance in personal relationships, and vigor in daily tasks among their children and students so that they may become well-adjusted in the society

Effects of fluoride and ethanol administration on lipid peroxidation systems in rat brain.

Exposure to fluoride and excessive ethanol consumption has been identified as a serious public health problem in many parts of the world, including India. Thus, the effect of co-exposure to fluoride and ethanol for 3-6 weeks was studied on lipid peroxidation (LPO) and oxidative stress related parameters in the rat brain. After 3 weeks, co-treated animals showed 95% increase in LPO levels compared to control. However, the levels of reduced glutathione, total and protein thiols were decreased. These changes were accompanied by a decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. Rats exposed to fluoride together with ethanol for 6 weeks resulted in 130% increase in LPO and decrease in the reduced glutathione levels. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase were reduced under these conditions. Brain histology revealed excessive lymphocytes, edema and spongeosis in the cortical region after six weeks of fluoride and ethanol treatment. These results suggest that exposure to fluoride together with ethanol enhances lipid peroxidation by affecting antioxidant defence systems in the rat brain.

Inhibition of dextransucrase activity in Streptococcus mutans by plant phenolics.

Streptococcus mutans is responsible for causing dental caries in humans and utilizes sucrose for its growth. The dextransucrase (EC 2.4.1.5) is responsible for sucrose metabolism, which exhibits both hydrolytic and glucosyltransferase activities. In this study, we examined the effects of the plant phenols, namely gallic, tannic and syringic acids and aqueous extracts of certain traditionally used chewing sticks (Acacia arabica, Azadirachta indica, Pongamia pinnata and Salvadora persica) for prevention of dental caries on hydrolytic activity of dextransucrsae in S. mutans. Gallic acid (4-5 mM) produced 80-90% inhibition of the enzyme, while tannic acid (0.2 mM) and syringic acid (5 mM) inhibited the enzyme activity 80% and 48%, respectively in vitro. The aqueous extracts of chewing sticks produced 35-40% inhibition of dextransucrase activity at 5 mg phenol concentration. Kinetic analysis revealed mixed-type of enzyme inhibition by polyphenols, where both Km and Vmax were altered. The value of Ki for tannic, gallic and syringic acids were 0.35, 1.6 and 1.94 mM, respectively. The enzyme inhibition by polyphenols was optimum at pH 7-7.5, while by plant extract was maximum at pH 5-6. These results suggest that plant polyphenols may find potential applications in the prevention and control of dental caries by inhibiting dextransucrase activity in S. mutans.

Dose and time related effects of lindane [gamma -hexachlorocyclohexane] on hair growth in rabbit

Background: One of the most effective 2nd line scabicidal agent lindane [gamma -HCH] is still used in many countries. It is moderately hazardous and causes severe physiological dysfunction in various organ systems

Method: The effects of [gamma -HCH] on hair growth of male orytolagus Cuniculus Rabbit was studied in variable doses of 5,10,15 and 25mg/kg body weight for short term [up to 14 days] and also long term [up to 30 days] exposure. In addition general conditions and also some hematoenzymatic parameters were recorded in unexposed and exposed [treated] animals

Results: There was gradual increase in loss of hair with increasing dose of Lindane. With 5mg/kg body weight mild hair loss in neck and trunk, 10mg/kg body weight mild patchy loss of hair in neck and trunk region, 15 mg/kg body weight marked patchy loss of hair in neck region and moderate patchy loss of hair in trunk region, 20mg/kg body weight patches of almost complete loss of hair all over the body was observed. In addition, dose and time related anorexia, diarrhea, behavioral changes [weakness, restlessness, excitement and hyperactivity], bleeding tendency [observed while taking blood] and enzymatic changes [significantly increased serum alkaline phosphatase and SGPT] were also observed

Conclusion: The pharmacological use of gamma -HCH, even as a 2nd line scabicidal agent should be strictly banned owing to its toxic effect on various systems of body

Modulation of intestinal brush border membrane chemical composition during postnatal development in rats : Effect of gestational diabetes.

There was a significant increase in fucose (52%), total hexoses (16%) and hexosamine (56%) except sialic acid, which was reduced (77%) in the microvillus membrane of infants born to rat mothers made diabetic by injecting alloxan on day 3 of gestation. Expressed on the protein basis there were a significant increase in membrane, triglyceride, total cholesterol, and phospholipids content of brush border in pups from diabetic group between 5-45 days of postnatal age. Intestinal morphology in diabetic group showed, regression of tubular glands, distorted cellular organization of mucosal cells, reduction in the mucosal cell height and number of secretory goblet cells. These findings suggest that the gestational diabetes affects the sugar and lipid composition of the intestinal brush border membrane in rats during early stages of the postnatal development, which may be associated with compromised tissue functions later in life.

Comparison of outcomes of membranous with endochondral bone graft in orbital floor reconstruction

Objective: To compare membranous with endochondral bone graft in orbital floor reconstruction in terms of donor site hematoma and correction of postoperative diplopia

Study Design: Randomized clinical trial

Place and duration of study: Department of Oral and Maxillofacial Surgery, King Edward Medical University / Mayo Hospital Lahore. One year from 01-07-09 to 30-06-10

Material and Method: 58 patients clinically and radiographically having defect in the orbital floor due to trauma were included in the study. According to the treatment, patients were randomly divided into two groups by lottery method. Group A [29 patients] received the membranous bone graft from calvariumand Group B [29 patients] received the endochondral bone graft from anterior iliac crest. The variables to be analyzed were donor site hematoma and post-operative diplopia

Results: Group A consisted of 29 patients [mean age 30.31years + 11.41] and Group B consisted of 29 patients [mean age 29.6 years + 9.05]. Donor site hematoma developed in 3 [10.3%] patients in Group A and in 9 [31.0%] patients in Group B. In Group A, postoperative diplopia persisted in 2 [6.9%] patients and in Group B, it persisted in 5 [17.2%] patients. Chi-Square test was used to compare the variables in both groups and the results were statistically significant for donor site hematoma [p value: 0.026] but insignificant for postoperative diplopia [p value: 0.113]

Conclusion: Membranous bone graft is better than endochondral bone graft in terms of donor site hematoma. When it comes to the correction of postoperative diplopia, there is no difference between two types of bone graft

Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients

CYP1A1 is the phase I enzyme that detoxifies the carcinogen or converts it into a more electrophilic form, metabolized by phase II enzymes like GSTP1. These detoxifying genes have been extensively studied in association with head and neck cancer (HNC) in different ethnic groups worldwide. The current study was aimed at screening genetic polymorphisms of genes CYP1A1 and GSTP1 in 388 Pakistani HNC patients and 150 cancer-free healthy controls, using PCR-SSCP. No already known variants of either gene were found, however a novel frameshift mutation due to insertion of T (g.2842_2843insT) was observed in the CYP1A1 gene. A statistically significant number (5.4 percent) of HNC cases, with the mean age of 51.75 (±15.7) years, presented this frameshift mutation in the conserved domain of CYP1A1. Another novel substitution mutation in was found in the GSTP1 gene, presenting TA instead of AG. The g.2848A > T polymorphism causes a leucine-to-leucine formation, whereas g.2849G > A causes alanine-to-threonine formation at amino acid positions 166 and 167, respectively. These exonic mutations were found in 9.5 percent of the HNC patients and in none of the controls. In addition, two intronic deletions of C (g.1074delC and g.1466delC) were also found in 11 patients with a mean age of 46.2 (±15.6) years. In conclusion, accumulation of mutations in genes CYP1A1 and GSTP1 appears to be associated with increased risk of developing HNC, suggesting that mutations in these genes may play a role in the etiology of head and neck cancer.

Ethanol-induced changes in lipid peroxidation of enterocytes across the crypt–villus axis in rats.

Background Reactive oxygen species (ROS) have been implicated in the turnover of epithelial cells in the rat intestine. The metabolism of ethanol generates ROS, which are implicated in cellular injury, but the levels of lipid peroxidation in intestine in chronic alcoholism are unknown. Aim To investigate the effects of ethanol ingestion on lipid peroxidation, and anti- and pro-oxidant enzyme systems in enterocytes across the crypt–villus axis in intestine. Methods Wistar rats (90–100 g) were administered 1 mL of 30% ethanol daily for 39 days. Intestinal epithelial cells were isolated in fractions. Malondialdehyde levels, and activities of glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase were determined in various cell fractions. Incorporation of H3- thymidine into DNA of enterocytes was also determined. Results Lipid peroxidation was elevated by two- to threefolds in both villus and crypt cells in ethanol-fed animals compared to controls. The activities of GST and GR were four- to six-folds higher in villus tip cells compared to crypt base cells. The activities of SOD and catalase were five- to seven-fold higher in crypt base cells compared to villus tip cells. Ethanol feeding elevated the activities of SOD (76-190%) and catalase (20-150%) in enterocytes all along the crypt–villus axis compared to the controls. H3 thymidine incorporation into DNA of enterocytes was reduced by half in ethanol-fed rats compared to controls. Conclusions There is a gradient in the concentration of lipid peroxides in enterocytes across the crypt–villus axis, being high at the villus tip and low at the crypt base in the rat intestine. Ethanol feeding enhanced lipid peroxidation in both villus and crypt cells.

Effect of gallic acid on alkaline phosphatase and peptidase activities in rat intestine.

Gallic acid is a normal constituent of many edible foods, thus directly interacts with epithelial tissue in intestine. In the present study, the effect of gallic acid on intestinal alkaline phosphatase (IAP) and peptidase activities in rat intestine was evaluated. Gallic acid (0.27-0.5 mM) inhibited activities of leucine aminopeptidase (LAP) and -glutamyl transpeptidase (-GTP) by over 90%, compared to controls in rat intestine. In contrast, 0.1-0.6 mM gallic acid either had no effect or stimulated the activity of IAP in rat intestine. The observed inhibition of peptidases by gallic acid was reversible in nature. Kinetic analysis revealed no change in Vmax of LAP (0.42-0.44 units/mg protein) and -GTP (0.22-0.24 units/mg protein), while the values of apparent Km were increased 6-7 fold, exhibiting competitive-type of enzyme inhibition by gallic acid. The values of Ki for LAP and -GTP were 0.037 mM and 0.017 mM, respectively. These observations indicate that gallic acid is a potent inhibitor of brush border peptidases, and thus may interfere in the digestion and absorption of proteins in the intestine.

Effect of Na+ ions on pH-dependent conformational changes in brush border sucrase-isomaltase in mice intestine.

Intestinal brush border sucrase-isomaltase (sucrose D-glucosidase E.C. 3.2.1.48, E.C. 3.2.1.10) exhibits pH-dependent stimulatory or inhibitory effects in response to Na+ ions. However, whether the enzyme undergoes conformational modulations as a function of pH and in the presence of alkali metal ions is not known. In this paper, we investigated the structural and functional relationship of purified murine sucrase in response to pH and Na+ ions using UV-CD fluorescence and spectroscopic studies. Kinetic studies revealed that at pH 5.0, the enzyme activation by Na+ ions was V-type, which changed to K-type at pH 7.2, whereas at alkaline pH (8.5), Na+ ions inhibited the enzyme activity and inhibition was uncompetitive in nature, affecting both the Km and Vmax components. Far UV-CD spectra of protein at pH 7.2 in the absence and presence of Na+ were almost overlapping, suggesting that secondary structure of protein was not affected upon addition of the salt. However, near UV-CD spectra indicated marked alterations in the tertiary structure of protein in presence of 50 mM Na+ ions. Increase in pH from 7.2 to 8.5 resulted in a marked rise in fluorescence intensity and red shift in lambda max due to tryptophan residues in the enzyme molecule. These findings suggested that alterations in enzyme activity as a function of pH and Na+ ions was associated with ionization of key amino acid residues together with structural modifications in the enzyme conformation around neutral or alkaline pH.

Prevention of hypotension in caesarean delivery under spinal anaesthesia; the combination of modified supine wedged position, crystalloid co-hydration and prophylactic atropine

To evaluate the efficacy of a modified supine wedged position with table tilt, crystalloid co hydration and prophylactic intravenous atropine in the prevention of hypotension in caesarean delivery under spinal anaesthesia. Phase 2 clinical trial. Place and Duration of Study: PAF Hospital Masroor Karachi and PAF Hospital Rafiqi Shorkot Oct 2005 - April 2006. 40 parturients undergoing elective caesarean section under spinal anaesthesia were studied. Lactated Ringer's solution 10 ml/kg was administered over 10min.After Spinal in the sitting position with a 25-gauge Quincke needle using0.75% hyperbaric bupivacaine [12.75-15mg], the parturient was placed in the modified supine position with table tilt .Atropine 10microg/kg was given i/v. The baseline blood pressure and heart rate in each parturient before intervention [crystalloid co hydration, spinal, modified supine wedged position and i/v atropine] were taken as control and evaluated against the values after the intervention at different time intervals. Thirty nine out of forty patients completed the study. Mean upper sensory level was T4 at 6min post spinal. The mean spinal to delivery time was less than 12 min.5% of the parturients developed hypotension at 2 min post spinal. The mean heart rate was 96/min. The mean, systolic and diastolic blood pressures remained close to the base line values at 4, 6, 10, 12, 16 and 20 min post spinal. Modified supine wedged position with table tilt, crystalloid co-hydration and prophylactic i/v atropine is an effective combination technique which prevents spinal induced hypotension in caesarean delivery

Effect of tannic acid on brush border disaccharidases in mammalian intestine.

Tannic acid is a glucoside (penta-m-digallolyl-glucose), which exhibits a wide variety of physiological functions. Around neutral pH, 0.4 mM tannic acid produced 84% inhibition of rat brush border sucrase activity, but 35-40% enzyme inhibition was observed in the rabbit intestine at 0.08 mM concentration. In the mice, 74-77% enzyme inhibition was observed at 0.05 mM concentration of tannic acid. The observed inhibition was reversible in rat intestine. Tannic acid (0.2 mM) also inhibited lactase (18% in adult and 71% in suckling animals), maltase (76%) and trehalase (88%) activities in rat intestine. pH versus activity curves showed that 0.2 mM tannic acid inhibited enzyme activity in rat by 91% at pH 5.5 which was reduced to 14% at pH 8.5 compared to the respective controls. In the rabbit 18-60% enzyme inhibition was noticed below pH 7.0, however at pH 8.5, it was of the order of 38%. Kinetic analysis revealed that tannic acid is a competitive inhibitor of rat brush border sucrase at pH 6.8. Effect of tannic acid together with various -SH group reacting reagents revealed that the enzyme inhibition is additive in nature, suggesting the distinct nature of binding sites on the enzyme for these compounds. The results suggest that tannic acid is a potent inhibitor of intestinal brush border disaccharidases, and could modulate the intestinal functions.

Demographic profile of patients with epilepsy in a community clinic

To study the Demographic profile of patients with Epilepsy. A descriptive study of five hundred patients with Epilepsy was counducted in, Ahbab Hospital, [Psychiatric Epilepsy clinic] Ravi Road, Lahore. All patients presented with seizures during that period were included in the study. Their detailed history and appropriate investigations were recorded on a study proforma. Epilepsy was classified according to EEG findings. Out of a total Five hundred patients with Epilepsy who visited Ahbab Hospital majority [62.9%] were of low socio-economic status and belong to rural areas of Pakistan. Males had Epilepsy [58%] more often compared to females [42%]. The most common type was Generalized Tonic Clonic Seizure.70% of the patients came with Epilepsy only, 13.0%were having Depression and 10.1%were Mental Retardation and 4.1%had a problem of Attention Deficit Hyperactive Disorder. The results of the study conclude that Epilepsy is more common among population with low socioeconomic status in the rural areas and dominantly involves the males.43% of the subjects were suffering from Generalized Tonic Clonic Seizures. The risk factors for developing Epilepsy include a positive family history of Epilepsy. Epilepsy is an important health problem. Identification of Demographic profile in a hospital setting will lead to more opportunities to improve preventive measures and quality of life in rural areas. It will also improve knowledge among rural backgrounds and health officials on the problems associated with this disease

Hypolactasia as a molecular basis of lactose intolerance.

Lactase-phlorizin hydrolase (LPH), a membrane-bound glycoprotein present in the luminal surface of enterocytes in the intestine is responsible for lactose intolerance, a phenomenon prevalent in humans worldwide. In the rodent intestine, the post-natal development of the LPH follows a specific pattern, such that the enzyme levels are high in the peri-natal period, but declines considerably upon maturation. The observed maturational decline in the LPH activity is very similar to adult-type hypolactasia observed in humans. Majority of the studies have been carried out using animal models or cell lines and a number of hypotheses have been put forward to explain the maturational decline of lactase activity such as: (a) decreased amount of lactase protein, (b) defect in post-translational modification of precursor lactase to the mature enzyme, and (c) synthesis of an inactive, high molecular weight lactase with altered glycosylation, however, the precise underlying mechanism of adult-type hypolactasia remains undefined. The present review describes the recent developments in understanding the regulation of lactase expression and the possible mechanism of adult-type hypolactasia, as a cause of lactose intolerance.

Susceptibility of lactase to luminal proteases in developing rat intestine.

BACKGROUND: Postnatal development of rat intestine is associated with a decline in brush-border lactase activity. This phenomenon is similar to the adulthood hypolactasia in humans. However, the mechanism underlying this process is not understood. METHODS: The effect of luminal proteases from adult rat intestine on the intestinal lactase activity in animals aged 7, 14, 21 and 30 days was studied in in vitro experiments. Lactase levels were estimated using enzyme assays and Western blot analysis. RESULTS: Incubation of purified brush borders with increasing concentrations of luminal proteases reduced the lactase activity in intestine of 7-day-old rats, but not in that of adult animals. Western blot analysis revealed low signal of the 220-kDa lactase protein in 7-day-old animals, but not that of older weaned animals. CONCLUSIONS: Our findings suggest that luminal proteases may be responsible for the maturational decline in intestinal lactase activity.

Characteristics and physiological role of surfactant-like particles secreted by entrocytes.

Intestinal epithelium secretes novel unilamellar membranes having characteristics similar to lung surfactants and thus has been named Surfactant-like particles (SLP). The chemical analysis of the membranes revealed cholesterol/phospholipid molar ratio of 0.68-0.78, which is much distinct from that of the underlying microvillus membranes (1.34-1.49). The membrane contains 4-6 proteins with a molar weight of 30-120 kDa and is enriched with alkaline phosphatase, contains low amounts of disaccharidases but no Na+, K(+)-ATPase activity. The secretion of SLP is stimulated by fat feeding. Chronic ethanol ingestion also induces the formation of SLP in rat intestine. A number of physiological functions have been attributed to SLP, which include: (i) as a protective lubricant in intestinal lumen, (ii) a role in triacylglycerol transport, (iii) as a vehicle for the transport of luminal proteins into blood, (iv) as a stratum for the adhesion of microorganisms in intestinal lumen, and (v) a role in trans-signalling mechanism across the basolateral surface of enterocytes.

In vitro translation of RNA to lactase during postnatal development of rat intestine.

mRNA levels encoding lactase were detected by Northern blot analysis using two different probes in developing rat intestine. Probe I and probe II corresponding to second half of prolactase gene showed a 6.8 kb mRNA transcript in 7, 14, 21 and 30 day old rat intestine. There was no change in quantity of lactase mRNA detected using probe II, but hybridization with probe I showed a progressive decrease in mRNA transcript encoding lactase with age. At day 7 and 14 of postnatal development, the lactase mRNA was quite high, but it reduced upon weaning. The in vitro translation products of RNA detected by Western blot analysis using brush border lactase antibodies showed several isoforms of lactase antigen with molecular weight ranging from 100-220 kDa. Analysed at days 7 and 30 of postnatal development, lactase isoforms of molecular weight 130 kDa and 220 kDa were similar to those found in purified brush border membranes. The translation of RNA to 220 kDa lactase protein was high in 7 and 14 day old pups, but it was markedly reduced in 30 day old animals. These findings support the contention that translation of mRNA to lactase is impaired in weaned animals, which may also be responsible for the maturational decline in lactase activity in adult rat intestine.

Postnatal development of alcohol dehydrogenase in liver and intestine of rats exposed to ethanol in utero.

BACKGROUND AND OBJECTIVES: Ethanol exposure during gestation induces marked aberrations in growth and development of offsprings collectively known as foetal alcohol syndrome (FAS);. However, its effects on the postnatal development of alcohol dehydrogenase (ADH) are not adequately investigated. Therefore, ADH activity in liver and intestine of rats exposed to ethanol during gestation was studied in relation to postnatal development. METHODS: Pregnant female rats beginning at day 1 of gestation were fed 1 ml of 30 per cent ethanol daily during the entire gestation period. ADH activity was determined in liver and intestine postnatally at day 4, 8, 14, 20 and 30. DNA and RNA contents and intestinal histology were also examined. RESULTS: During the first two weeks of postnatal life, there was no difference in ADH levels of rat liver and intestine in control and prenatally ethanol exposed pups but ADH levels were significantly reduced at 3-4 wk in ethanol fed group compared to control. A similar decrease in DNA and RNA contents of intestine and changes in tissue morphology were observed in ethanol exposed pups during postnatal development. INTERPRETATION AND CONCLUSION: The findings of our study suggested that prenatal ethanol exposure modified ADH activity in liver and intestine during postnatal development. This could affect ethanol metabolism under these conditions.