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This study explores the differences between British English and Pakistani English speakers regarding the use of aspiration in unvoiced plosives-bilabial, alveolar and velar- at syllable initial position in both stressed and unstressed syllables through a quantitative and statistical analysis of acoustic co-relate of aspiration-VOT. Such differences may account for establishing and describing the phonetic features of Pakistani English as a non-native/ESL variety of English. It is hypothesized that unlike British English speakers, Pakistani English speakers do not use aspiration at stressed syllable initial positions as an allophonic variety of voiceless stops. 30 university graduates from Seraiki, Punjabi and Urdu languages (10 from each) were given a wordlist (Stimuli) comprising 60 words in the citation form to read out and the VOT values from their recordings were extracted using wavesurfer software. These values were then compared with the values from BE speakers' data. The acoustic analyses showed that there is a stark difference of VOT between BE and PE speakers as PE speakers' highest range of production of bilabial, alveolar and velar plosives at stressed and unstressed position does not go beyond 37 ms as compared to BE speakers' highest range of 94 ms. BE speakers vary in their VOTs at stressed and unstressed syllable initial positions using aspiration at stressed syllable initial positions but PE speakers do not show any variation in VOT at both the positions proving that they do not use aspiration at all at any position. A universal phenomenon observed is the rise in VOT values from bilabial to alveolar and alveolar to velar positions in both PE and BE speaker data. [ABSTRACT FROM AUTHOR]

Objective: Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL) of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan. Methods: This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18-65 years) suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ≥4). Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale--Short Form (pain severity score and pain interference score). QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs) and serious AEs. Results: Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD]) pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001). The mean (± SD) pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001). There was a decrease of ≥30% in the pain severity score between visits. The mean (± SD) QoL scale score improved from 5.9±1.6 at baseline to 8.0±1.7 at week 12. A total of ten (2.2%) patients reported AEs during the study period. No patient discontinued the study due to AEs. Conclusion: In this real-life experience study, carbamazepine, when prescribed for 12 weeks to adult diabetic patients suffering from neuropathic pain, showed pain-relief effect, with reduced mean pain severity and mean pain interference scores and with improved QoL and good tolerability profile. [ABSTRACT FROM AUTHOR]

ABSTRACT There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium. Intraepithelial capillaries surrounded by thick collagen were also present. Gap junctions between myocytes were interrupted or extensively widened with reduced mitochondria and caveolae. Collagen accumulation, degenerated nerve fibres and myelin bodies were seen between myocytes with increased collagen content and frequent mast cells, phagocytes and lymphocyte aggregates in the stroma. All ultra-structural lesions became augmented with longer duration of diabetes. Diabetes induces time-dependent pathologic changes in the urinary bladder of rats that might account for bladder dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of deep intramuscular methylprednisolone (IMMP) in the treatment of recurrent scleritis. Methods: A total of 15 patients with scleritis (12 anterior, 3 pan) underwent IMMP injection deep into the thigh. Thirteen patients were already being treated with oral non-steroidal anti-inflammatory drugs, oral prednisolone, an oral immunosuppressive agent, or a combination of these drugs. A second IMMP injection was given to nine patients, making a total of 24 injections. Follow-up ranged from 4 to 18 months. Results: There was a documented improvement in scleritis after 21/24 (87.3%) injections with a mean duration of improvement of 5.7 months. No patient required the introduction of oral corticosteroid or immunosuppressive agent, and only one patient required an increase in methotrexate to control the disease. No systemic, injection site, or ocular side effects were noted. Conclusions: Deep IMMP is a safe and effective treatment for scleritis. It ensures compliance, avoids the systemic side effects of oral corticosteroids, and is easily repeatable in the outpatient setting. [ABSTRACT FROM AUTHOR]

Background: To compare buccal midazolam with rectal diazepam in status epilepticus in terms of recurrence of seizures and risk for treatment failure Methods: In this randomized controlled study a total of 410 children with status epilepticus irrespective of cause were included. Patients were randomly divided into two groups. Patients in group A (n=205) were treated with buccal midazolam 0.3 mg/kg/dose and patients in group B (n=205) were treated with rectal diazepam 0.3 mg/kg/dose. Both groups were observed for duration of controlling of seizures within 10 minutes to see the risk for treatment failure and to check for recurrence of seizure within one hour after initial control of seizure. Results: The average age of the patients was 4.66±2.95 years. Mean age was not significant between groups while mean duration of control of seizure was significant between groups. Recurrence was significantly high in group B as compared to group A. Group A was more effective than group B because the recurrence rate was low and treatment was significantly effective (p=0.002). Conclusion: - Buccal midazolam offers a promising alternative to rectal diazepam for the treatment of seizures in children. [ABSTRACT FROM AUTHOR]

Objective: To audit the practices involved in blood component transfusion in the management of patients in the paediatric intensive care unit of our hospital and to determine the appropriateness of transfusion after comparing them with clinical practice guidelines recommended by Royal Children's Hospital (RCH). Materials and Methods: All patients admitted to pediatric intensive care who were managed with blood component transfusions were retrospectively audited for 8 weeks. Management details including indications of transfusion and its appropriateness were recorded. Clinical practice guidelines recommended by Royal Children's Hospital (RCH) were used as standards. Results: One hundred and ninety-two transfusions were done during the study period out of which 58 percent were done to males and 41 percent to females. Most transfusions were done in infants (44%) and O Positive blood group was found rampant among blood groups of all recipients (33.3%). Red cell concentrates were predominantly (55.7%) and appropriately (72%) for transfusion among all blood components. Platelet concentrates were most inappropriately transfused (57%) followed by fresh frozen plasma (54%) and red cell concentrates (27%). There was a significant percentage of inappropriate transfusion of all blood components (p=0.00). Conclusion: All blood components were significantly found inappropriately transfused, the commonest component being platelet concentrates. [ABSTRACT FROM AUTHOR]

Background : To compare magnesium sulfate with placebo in term neonates with moderate to severe ischemic encephalopathy due to severe perinatal asphyxia in term of improved neurological outcome. Methods: In this randomized controlled trial a total of seventy term neonates of age less than six hours of either sex suffering from moderate and severe hypoxic ischemic encephalopathy were included. Neonates were assessed at two different ages , 2-3 hours and 4-5 hours, respectively. Each patient remained in the hospital for at least 14 days. Patients were randomly divided into two groups A and B. Group A received magnesium sulphate at 250 mg/kg/dose ( 1 ml/kg/ dose in 20 ml of 5% dextrose water) over one hour with the additional doses repeated at interval of 24 hours and 48 hours. Group B received 1 ml/kg/dose of normal saline in 20 ml of 5% dextrose water. (Three doses , 24 hours apart). Serum magnesium levels were carried out at seventy two hours of life. .Monitoring was also done for clinical course of encephalopathy, laboratory variables and adverse effects. At the time of discharge ,neurological examination was carried out and CT scan was done at fourteenth day of life. Results:- More infants in group A were sucking at discharge as compared to group B (71.4. vs 40.; p=0.008). Neuroimaging (CT scan on day 14th) yielded abnormal findings for fewer neonates in group A which was significantly low as compared to group B (11.4% vs 37.1. p= 0.012). Conclusion: Postnatal magnesium sulfate infusion is effective in improving outcome for infants with severe perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Soil salinity among other abiotic stresses is a major threat to cultivated land. Breeding salt tolerant cultivars has always been thought to be an effective and cheaper way to overcome salinity problem. Salt tolerant and salt sensitive wheat accessions were hybridized to develop genetic material to investigate inheritance of salt tolerance based on early seedling, adult plant and physiological responses. Salt tolerance in low salinity appeared to be a complex polygenic trait. However, genetic models for most responses were poor fit in high salinity and suggested further investigations. Differences in gene expressions in different NaCl concentrations appeared to be due to different gene regulation or interaction and/or involvement of additional or hidden genes. Both additive and non-additive gene effects required to be considered while designing of breeding programme for improving salt tolerance in wheat and in the statistical model used to find QTL for the salt tolerance. This QTL couple with recurrent selection for specific combining ability of the 4WLRG/1-8 with an excellent cultivar of wheat appears to be a good salt tolerant breeding strategy. © 2014 Friends Science Publishers [ABSTRACT FROM AUTHOR]

Purpose: To develop modified release microcapsules of flurbiprofen for sustained release and reduced gastrointestinal side effects. Method: A co-polymer containing Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC) in different drug/co-polymer ratios was used for microencapsulation of flurbiprofen by modified emulsion solvent evaporation (MESE) technique. The microcapsules were evaluated by x-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR) and scanning electron microscopy (SEM). Dissolution study was conducted in 0.1 M HCl for 2 h and phosphate buffer (pH 7.4) for 8 h, and the resulting data were analyzed by various pharmacokinetic models. Results: The data obtained from pre-formulation confirmed the purity of flurbiprofen. Particle size, flow rate and angle of repose showed good flow properties. FTIR and DSC confirmed the absence of incompatibilities among the drug and polymers. XRD of flurbiprofen showed characteristic sharp peaks confirming the crystalline nature of the drug which, however, decreased slightly in the formulation. SEM revealed that microencapsules of spherical shape and rough surface were produced at lower drug to co-polymer ratio in contrast to the higher ratio which produced irregular microcapsules. Encapsulation efficiency was 65 - 85 % while regression coefficient (R2) values from kinetic analysis showed that release followed Korsmeyer-Peppas model with "n" > 1 indicating release mechanism followed super case II transport. Conclusion: MESE technique using Eudragit RS 100/HPMC polymer blend is a suitable approach to development of modified release flurbiprofen microcapsules. [ABSTRACT FROM AUTHOR]

Background: Gastroparesis is a serious condition that can be caused by diabetes, surgery or infection, or can be idiopathic. When there is no mechanical obstruction, gastroparesis is characterized by delayed stomach emptying. Itopride, a prokinetic drug, inhibits acetylcholinesterase activity in addition to antagonizing dopamine D2 receptors., Methods: This prospective, multicentre study is based on real-world data from 988 patients with a diagnosis of diabetic gastroparesis for index (PAGI-SYM2) evaluation at baseline and week 4 of treatment for upper gastrointestinal disorder symptoms., Results: Upper gastrointestinal symptom severity scores improved significantly after 4 weeks of treatment ( p <0.001), with significant improvement across all categories of gastroparesis (very mild (37-58.6%), mild degree (24.6-31.6%), moderate (29.3-7.3%) and severe (8.8-2.6%)., Conclusion: Itopride SR (Nogerd SR) in a 150 mg once-daily dose showed promising results in reducing the severity of upper gastrointestinal disorder symptoms associated with diabetic gastroparesis. Both statistical and clinical effectiveness were observed. Moreover, the treatment demonstrated a favourable tolerability profile, with a low incidence of adverse effects., Competing Interests: Disclosure and potential conflicts of interest: NM is a full-time employee of Helix Pharma Pvt. Ltd. All authors has received support for attending meetings and/or travel from Helix Pharma. The remuneration was given to the investigators for examining and entering the data during the study duration. The authors report no other conflicts. The honesty of the study was not traded for any monetary benefit. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/09/dic.2023-6-4-COI.pdf, (Copyright © 2023 Ramzan A, Memon GF, Shaikh AA, Khoso MM, Meher T, Ghafoor A, Shehzad NA, Ahmed S, Nawaz Z, Rehan M, Saeed T, Taj W, Abbass S, Khan R, Ehsan H, Alam A, Manzoor B, Khan MN, Yahya KM, Mukhtiar F, Javed MA, Sheikh MU, Janjua D, Jabeen S, Zafar J, Khokhar RH, Nazar M, Maheshwary N, Khan MA.)

Transforming growth factor beta1 (TGFβ1) and matrix metalloproteinase-9 (MMP-9) have been associated with migration and invasion in hepatocellular carcinoma (HCC). Recent studies have suggested a positive feedback loop between TGFβ1 and MMP-9 mediated by the PI3K signaling pathway that confers acquired invasion and metastasis in HCC via induction of the epithelial-mesenchymal transition (EMT), which grows into invasive carcinoma. But the potential molecular mechanism of this loop on HCC has not been clarified yet. Therefore, this study is designed to explore the association between the two entities and their key determinants such as NFκB, TIMP-1, and hepatic stellate cells (HSCs). Hence, a qualitative modeling framework is implemented that predict the role of biological regulatory network (BRN) during recovery and HCC metastasis. Qualitative modeling predicts discrete trajectories, stable states, and cycles that highlight the paths leading to disease recovery and homeostasis, respectively. The deadlock stable state (1, 1, 1, 1, 1) predicts high expression of all the entities in the BRN, resulting in the progression of HCC. The qualitative model predicts 30 cycles representing significant paths leading to recovery and homeostasis and amongst these the most significant discrete cycle was selected based on the highest betweenness centralities of the discrete states. We further verified our model with network modeling and simulation analysis based on petri net modeling approach. The BRN dynamics were analyzed over time. The results implied that over the course of disease condition or homeostasis, the biological entities are activated in a variable manner. Taken together, our findings suggest that the TGFβ1 and the MMP-9 feedback loop is critical in tumor progression, as it may aid in the development of treatment strategies that are designed to target both TGFβ and MMP-9.

The liquid and semisolid matrix technology, filling liquids, semi-solids and gels in hard gelatin capsule are promising, thus, there is a need of enhanced research interest in the technology. Therefore, the present study was aimed to investigate isoniazid (freely soluble) and metronidazole (slightly soluble) gels filled in hard gelatin capsules for the effect of poloxamers of different viscosities on release of the drugs. Gel of each drug (10% w/w, particle size 180-250 μm), prepared by mixing poloxamer and 8% w/w hydrophilic silicon dioxide (Aerosil® A200), was assessed for rheology, dispersion stability and release profile. Both the drugs remained dispersed in majority of gels for more than 30 days, and dispersions were depended on gels' viscosity, which was further depended on viscosity of poloxamers. A small change in viscosity was noted in gels on storage. FTIR spectra indicated no interactions between components of the gels. The gels exhibited thixotropic and shear-thinning behaviour, which were suitable for filling in hard gelatin capsules without any leakage from the capsules. The release of both drugs from the phase-stable gels for 30 days followed first-order kinetics and was found to be correlated to drugs' solubility, poloxamers' viscosity, polyoxyethylene contents and proportion of block copolymer (poloxamers) in the gels. The findings of the present study indicated that release of drugs of different solubilities (isoniazid and metronidazole) might be modified from gels using different poloxamers and Aerosil® A200.

Cellular homeostasis is a continuous phenomenon that if compromised can lead to several disorders including cancer. There is a need to understand the dynamics of cellular proliferation to get deeper insights into the prevalence of cancer. Mechanistic Target of Rapamycin (mTOR) is implicated as the central regulator of the metabolic pathway involved in growth whereas its two distinct complexes mTORC1 and mTORC2 perform particular functions in cellular propagation. To date, mTORC1 is a well defined therapeutic target to inhibit uncontrolled cell division, while the role of mTORC2 is not well characterized. Therefore, the current study is designed to understand the signaling dynamics of mTOR and its partner proteins such as PI3K, PTEN, mTORC2, PKB (Akt), mTORC1, and FOXO. For this purpose, a qualitative model of mTOR-associated Biological Regulatory Network (BRN) is constructed to predict its regulatory behaviors which may not be predictable otherwise. The depleted expression of PTEN and FOXO along with the overexpression of PI3K, mTORC2, mTORC1 and Akt is predicted as a stable steady state which is in accordance with their observed expression levels in the progression of various cancers. The qualitative model also predicts the homeostasis of all the entities in the form of qualitative cycles. The significant qualitative (discrete) cycle is identified by analyzing betweenness centralities of the qualitative (discrete) states. This cycle is further refined as a linear hybrid automaton model with the production (activation) and degradation (inhibition) time delays in order to analyze the real-time constraints for its existence. The analysis of the hybrid model provides a formal proof that during homeostasis the inhibition time delay of Akt is less than the inhibition time delay of mTORC2. In conclusion, our observations characterize that in homeostasis Akt is degraded with a faster rate than mTORC2 which suggests that the inhibition of Akt along with the activation of mTORC2 may be a better therapeutic strategy for the treatment of cancer.

Dengue virus can ignite both protective and pathogenic responses in human. The pathogenesis is related with modified functioning of our immune system during infection. Pattern recognition receptors like Toll like receptor 3 is vital for the induction of innate immunity in case of Dengue infection. Toll like receptor 3 induces TRIF mediated activation of Type 1 interferons and Fc receptor mediated induction of cytokines. Interferons have been related with clearance of Dengue virus but it has adopted modified regulatory mechanisms to counter this effect. SOCS protein is also induced due to the interferon and cytokine mediated signalling which can subsequently play its part in the regulation of interferon and cytokine production. Our hypothesis in this study relates the pathogenesis of Dengue virus with the SOCS mediated inhibition of our innate immunity. We used the qualitative formalism of René Thomas to model the biological regulatory network of Toll like receptor 3 mediated signalling pathway in an association with pathogenesis of dengue. Logical parameters for the qualitative modelling were inferred using a model checking approach implemented in SMBioNet. A linear hybrid model, parametric linear hybrid automaton, was constructed to incorporate the activation and inhibition time delays in the qualitative model. The qualitative model captured all the possible expression dynamics of the proteins in the form of paths, some of which were observed as abstract cycles (representing homoeostasis) and diverging paths towards stable states. The analysis of the qualitative model highlighted the importance of SOCS protein in elevating propagation of dengue virus through inhibition of type 1 interferons. Detailed qualitative analysis of regulatory network endorses our hypothesis that elevated levels of cytokine subsequently induce SOCS expression which in turn results into the continuous down-regulation of Toll like receptor 3 and interferon. This may result into the Dengue pathogenesis during the stage of immunosuppression. Further analysis with HyTech (HYbrid TECHnology) tool provided us with the real-time constraints (delay constraints) of the proteins involved in the cyclic paths of the regulatory network backing the evidence provided by the qualitative analysis. The HyTech results also suggest that the role of SOCS is vital in homoeostasis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties.

Background: This study aimed to formulate a water-in-oil emulsion (formulation) of Terminalia chebula versus its vehicle (base) as control, and investigate its effects on skin melanin, skin erythema, skin moisture content, and transepidermal water loss (TEWL)., Material and Methods: Base containing no active material, and formulation containing 5% concentrated extract of T. chebula, were developed. Different stability parameters were monitored at 8, 25, and 40 °C, as well as 40 °C + 75% relative humidity, for a period of 4 weeks. It was concluded that the creams remained stable at all storage conditions. Both base and formulation were applied to the cheeks of human volunteers for a period of 8 weeks. Different skin parameters were monitored every week to measure any effect produced by these creams., Results: Changes in TEWL produced by base and formulation were insignificant (p > 0.05) with respect to time while significant (p ≤ 0.05) with respect to base and formulation. The skin moisture content increased after the application of formulation throughout the study period; this effect was insignificant (p > 0.05) with respect to time while significant (p ≤ 0.05) with respect to base and formulation. Both base and formulation showed insignificant (p > 0.05) effects on skin melanin content with respect to time. Skin erythema was reduced by the formulation. Both base and formulation produced statistically insignificant (p > 0.05) effects on skin sebum., Conclusion: Both creams were aesthetic with respect to sensory evaluation. T. chebula topical cream showed a positive rejuvenating effect on human skin. Hopefully, this study will encourage more attention towards the research and utilization of herbal medicines., (Copyright © 2012 S. Karger AG, Basel.)

Background and Objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome., Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome., Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(9)/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome., Conclusions: This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

This study was designed to evaluate the hypoglycemic effects of different plant extracts in single and in combined formulation, in experimentally induced "diabetic rabbits". The extracts were obtained from seeds of Syzygium jambolana, fruits of Momordica charantia and leaves of Azadirachta indica. Treatment of diabetes with plant extracts was started at 8 days after alloxan injection. Rabbits were randomly divided into four groups, each group consisting of six rabbits. Each group of rabbits was given a dose of granules containing 200 mg/kg b.w. concentrated ethanolic extract of a plant while the fourth group was given a dose of granules consisting of combined extract of all three folk plants. Blood samples were drawn at 0, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h. Serum glucose estimation was done by glucose oxidase kit method. Anti-diabetic effect was produced after 72 h in groups 1, 2 and 3 that were administered with a dose of granules of ethanolic extract of single plant but in group 4, treated with 200 mg/kg body weight of combined extract of all three plants, hypoglycemic effect was produced after 96 h. Hypoglycemic effects may be induced in rabbits by administration of extracts of various plant parts. The hypoglycemic effect produced by granules of single plant extract was more pronounced than antidiabetic effect produced by combining three extracts in a single formulation.

Background and Aims: We studied longterm application of cream containing green tea extract, to obtain knowledge of its effects on epidermal mechanics by 2-mm diameter Cutometer probe., Methods: Using this non-invasive device, we assessed the effects of green tea extract cream on skin mechanical properties. Healthy male volunteers (n=10) were included in this study, which lasted 60 days. The biomechanical properties of the skin were examined by a non-invasive suction device (Cutometer) and the cheeks were defined as the test area., Results: Statistically significant (p<0.05) results were notable for the R6 (Uv/Ue) parameter with respect to time (ANOVA); R0, R2 (Ua/Uf) and R7 (Ur/Uf) parameters were found statistically not significant by ANOVA. This study demonstrates that green tea formulation has a certain effect on R6 (Uv/Ue) parameter when applied regularly for a certain period of time., Conclusions: These results indicate that the formulation has no pronounced overall effects on skin elastic or biological properties, but significant R6 (Uv/Ue) values indicate that it does have definite effects on the viscoelastic properties of the skin.

Background/aims: Documentation of conjunctival forniceal foreshortening in cases of progressive cicatrising conjunctivitis (PCC) is important in ascertaining disease stage and progression. Lower fornix shortening is often documented subjectively or semi-objectively, whereas upper forniceal obliteration is seldom quantified. Although tools such as fornix depth measurers (FDMs) have been described, their designs limit upper fornix measurement. The purpose of this study was to custom-design a FDM to evaluate the upper fornix and to assess variability in gauging fornix depth., Methods: A polymethylmethacrylate FDM was constructed using industry-standard jewellery computer software and machinery. Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland-Altman plots., Results: Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (±2SD) of -15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, ±1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between -2 and +3 mm., Conclusions: This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring.

The C57BL/6J mice are inbred strains and develop the metabolic syndrome of obesity, hyperinsulinemia, hyperglycemia, and hypertension, when fed a high-fat diet. These features are similar to those observed in the human metabolic syndrome. This article examined the effect of fat-enriched (FE) diet on the pattern of distribution of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-positive cells in the pancreatic islets of C57BL/6J mice using immunohistochemical methods. Insulin-immunoreactive cells were observed in both the peripheral and central regions of the islets of Langerhans in both FE- and control diet-fed mice. The percentage distribution of insulin-positive cells was similar in FE (83.5 +/- 6.4) compared to control diet-fed C57BL/6J mice (83.8 +/- 6.5). Glucagon-containing cells were discerned in the periphery of pancreatic islets in both FE- and control diet-fed mice. The percentage distribution of glucagon was not statistically different in mice fed with FE (9.9 +/- 2.7) compared to control diet (11.3 +/- 4.9). Somatostatin-positive cells were seen in the outer part of the islet of Langerhans and constitute 12.1% (+/-6.3) and 10% (+/-5.5) of pancreatic islet cells in FE- and control diet-fed mice, respectively. PP-immunoreactive cells were observed in the peripheral region of the pancreatic islets of both FE- and control diet-fed mice. The percentage distribution of PP-positive cells was significantly (2.0 +/- 1.2) lower compared to control (5.1 +/- 2.4). In conclusion, the number of PP is significantly reduced in FE diet-fed mice and may play a role in the pathogenesis of diet-induced metabolic syndrome in C57BL/6J mice.