Use of Drugs Considering Route of Administration on Drug Prescription Pattern for Bronchial Asthma in a Tertiary Level Hospital.

Bronchial asthma is one of the much known long-term respiratory conditions. Incidence is increasing, in developing countries like Bangladesh. Cross-sectional type of observational study was carried out over one year (July 2017 to June 2018) in the department of Pharmacology with collaboration of the department of Respiratory Medicine and Medicine, Mymensingh Medical College and Hospital, Mymensingh, Bangladesh. A total of 160 patients were selected non-randomly for the study. Inhalation route (52.35%) was the most preferred one over oral route (47.65%). In total 245 drugs, 131 FDC drugs (Salmeterol + Fluticasone) were prescribed with inhalation therapy which is 53.46%, another 9 FDC drugs that is (Ipratropium bromide + Salbutamol) were prescribed with inhalation therapy which is 3.67%, 101 drugs (Salbutamol) were prescribed with inhalation therapy that is 41.23%, 4 drugs (Beclomethasone) were prescribed with inhalation therapy that is 1.64%. Majority of patient were taking inhalation form of anti-asthmatic drugs.

Metabolic Syndrome: An Indicator of Complicated Gall Stone Disease?

Background Gallstone disease is a common surgical entity worldwide and accounts for a major portion of hospital admissions and surgeries. Metabolic syndrome is diagnosed when three of the following medical conditions are positive: central obesity, high blood pressure, increased fasting glucose levels, low high-density lipoprotein (HDL) levels and high serum triglycerides. Objective To compare the frequency of metabolic syndrome in patients with uncomplicated gallstone disease and complicated gallstone disease. Study design Observational, cross-sectional study. Methodology A total of 104 patients, above age 18 years, visiting the outpatient department (OPD) or the emergency department, diagnosed as having gallstone disease. The study was conducted in surgical unit VI, civil hospital Karachi from June 2014 to June 2015. Patients' demographics, abdominal waist circumference, blood pressure, serum fasting blood sugar, triglyceride level and HDL levels were recorded. Final outcome was labeled as presence or absence of metabolic syndrome. Presence of metabolic syndrome was compared in patients with complicated gallstone disease as well as in patients with uncomplicated gallstone disease. Chi square test was used to detect statistical significance and a p-value of <0.05 was taken as significant. Results The ages were comparable between the two groups, that is, the complicated and uncomplicated gallstone disease at 42.42 +/- 12.15 years in the former and 39.24 +/- 10.41 years in the latter group. Metabolic syndrome was more predominant in the complicated arm 40.38% when compared to uncomplicated arm 25% but it was not significant statistically with a p-value of 0.2. Conclusion Metabolic syndrome is associated with complicated gallstone disease though this study failed to reach statistical significance due to small sample size, it re-enforces the findings of previous studies. It is an easily assessable and useful measure to predict complications associated with gall stone disease.

Fabrication of graphene/gold-modified screen-printed electrode for detection of carcinoembryonic antigen.

Immunosensors based on gold nanoparticles and reduced graphene oxide (AuNPs/rGO)-modified screen-printed electrodes (SPEs) were successfully synthesized using an electrochemical deposition method. The modified SPEs were characterized using a field emission scanning electron microscope (FESEM) and Raman spectroscopy to analyze the morphology and composition of AuNPs and rGO. Both the FESEM and Raman spectroscopy revealed that the AuNPs were successfully anchored on the thin film of rGO deposited on the surface of the SPEs. Characterization with a ferri-ferrocyanide couple [Fe(CN)6(3-/4-)] showed that the electron transfer kinetic between the analyte and electrode was enhanced after the modification with the AuNPs/rGO composite on the electrode surface, in addition to increasing the effective surface area of the electrode. The modified SPE was immobilized with a sandwich type immunosensor to mimic the ELISA (enzyme-linked immunosorbent assay) immunoassay. The modified SPE that was fortified with the sandwich type immunosensor exhibited double electrochemical responses in the detection of carcinoembryonic antigen (CEA), with linear ranges of 0.5-50 ng/mL and 250-2000 ng/mL and limits of detection of 0.28 ng/mL and 181.5 ng/mL, respectively.

Fabrication of an electrochemical sensor based on carbon nanotubes modified with gold nanoparticles for determination of valrubicin as a chemotherapy drug: valrubicin-DNA interaction.

In this study, an electrochemical sensor was fabricated based on gold nanoparticles/ ethylenediamine/ multi-wall carbon-nanotubes modified gold electrode (AuNPs/en/MWCNTs/AuE) for determination of valrubicin in biological samples. Valrubicin was effectively accumulated on the surface of AuNPs/en/MWCNTs/AuE and produced a pair of redox peaks at around 0.662 and 0.578V (vs. Ag/AgCl) in citrate buffer (pH4.0). The electrochemical parameters including pH, buffer, ionic strength, scan rate and size of AuNPs have been optimized. There was a good linear correlation between cathodic peak current and concentration of valrubicin in the range of 0.5 to 80.0µmolL(-1) with the detection limit of 0.018µmolL(-1) in citrate buffer (pH4.0) and 0.1molL(-1) KCl. Finally, the constructed sensor was successfully applied for determination of valrubicin in human urine and blood serum. In further studies, the different sequences of single stranded DNA probes have been immobilized on the surface of AuNPs decorated on MWCNTs to study the interaction of oligonucleotides with valrubicin.

Comparison of ultrasonography with computed tomography in the diagnosis of nasal bone fractures.

OBJECTIVES: The aim of this study is to compare ultrasonography with CT in the diagnosis of nasal bone fractures. METHODS: 40 patients (9 female and 31 male) with mid-facial fractures, which were suspected nasal bone fractures, were included. All of the patients had mid-facial CT images. Ultrasonography with a 7.5 MHz transducer (Aloka 3500, Tokyo, Japan) was used to evaluate the nasal bone fractures. All of the sonograms were compared with CT findings for sensitivity, specificity and predictive values. A χ(2) test was applied to the data to assess statistical significance. RESULTS: CT diagnosed nasal bone fractures in 24 of the 40 patients (9 unilateral fractures and 15 bilateral fractures) while ultrasonography diagnosed the fractured bones in 23 patients (9 unilateral fractures and 14 bilateral fractures). Ultrasonography missed one fractured bone in a bilateral fractured case and a unilateral fracture was also missed (two false-negative results). The sensitivity and specificity of ultrasonography in assessing nasal bone fracture in comparison with CT were 94.9% and 100%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) of ultrasonographic evaluation of the nasal bone fractures were 100% and 95.3%, respectively. The χ(2) test did not show any significant difference between CT and ultrasonography in diagnosis of nasal bone fractures (P = 0.819). CONCLUSION: Ultrasonography can be used as a first line of diagnostic imaging for evaluating nasal bone fractures, especially in children and pregnant women.

Study on the prevalence of dairy cattle lameness and its effects of production indices in Iran. A locomotion scoring base study.

In this current study, prevalence of lameness was detected and its changes during different parities, Days in Milk (DIM) and milk production were studies. In addition, effects of lameness on Open Days (OD) and Service per Conception (S/C) were studied. Three dairy farms on three scales (1: Large, approximately 900 milking cows, 2: Medium, approximately 100 milking cows and 3: Small, approximately 20 milking cows) were watched for lameness in 2005-2006. Locomotion Scoring (LS) by Sprecher method (1-5 point scale) has been done by videoing of the animals at the exit of the milking parlor. Videos were reviewed by two expert and mean of the each score used as score of the animal, cows with scores 1 and 2 recorded as non-lame and 3, 4 and 5 as lame cows. The average score of the lameness in autumn and spring recorded as 2.47 and 2.73, respectively that was higher significantly in spring. LS has been increased significantly by increasing parity and DIM, as highest scores were recorded in parity 4 and DIM 240-300. No significant differences between lame and non-lame cows were recorded in according to their milk production. The highest (percent in lame cows) scores were recorded in high producing cows. No significant difference in milk production has been recorded in different LS. However the average production of milk in lame cows were 1.08 L day(-1) less that non-lame cows. The average OD of the lame cows was significantly longer (52 days) than non-lame cows. Lame cows needed significantly higher service/conception (one) than non-lame cows. Median of OD and S/C has been increased by LS.

Fatal cellulitis caused by Apophysomyces elegans.

A case of cellulitis of the left lateral side of the face caused by the zygomycete Apophysomyces elegans in a healthy male following a road traffic accident is reported. The contaminated soil was the source of fungus. Broad aseptate fungal hyphae were seen in the necrosed tissues. Extensive tissue debridement and treatment with amphotericin B were not successful in controlling the rapid invasion of the tissues by the fungus. Patient developed angioinvasion, severe cellulitis and finally succumbed to the infection three weeks after admission.

Multiple discharging sinuses: an unusual presentation caused by Absidia corymbifera.

A case of zygomycosis presenting with non-healing multiple discharging sinuses in a diabetic patient is reported here. The debrided tissue on histopathological examination revealed dense infiltration with aseptate fungal hyphae. Potassium hydroxide mount showed hyaline aseptate hyphae suggestive of zygomycosis. On culture, Absidia corymbifera was isolated. The patient responded to surgical debridement and therapy with amphotericin B followed by itraconazole.

Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide.

AIMS: To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension. METHODS: This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy. RESULTS: Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101). CONCLUSION: Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.

Frog PNKT-4B cells express specific extracellular matrix-degrading enzymes and cytokines correlated with an invasive phenotype.

A temperature-dependent metastatic phenotype reported for a frog cell line, PNKT-4B, provided a means for studying potential mediators of cell-matrix interaction involved in metastatic invasion. Zymography revealed that these cells secreted enzyme species with properties and characteristics of mammalian metalloproteinases: collagenase, stromelysin, gelatinase A, and gelatinase B. These enzymes were produced by PNKT-4B cultures maintained at both invasive-permissive (28 degrees C), and invasion-restrictive (20 degrees C) temperatures. However, under the invasive-permissive culture condition cells produced more of the putative gelatinase B and A enzymes. In addition, an activated form of gelatinase A was produced only in invasion-permissive cultures. DNA synthesis bioassays (Mv1Lu cell line and mouse thymocytes) to detect growth promoting and/or inhibitory cytokines, revealed that PNKT-4B cultures kept at 28 degrees C released significantly higher levels of stimulatory (interleukin-1-like) and latent inhibitory (transforming growth factor-beta-like) substances into the medium compared to 20 degrees C cultures. Pre-absorption of media samples with heparin-sepharose indicated a second stimulatory cytokine as well. A corneal fibroblast bioassay that tests for mediators of collagenase synthesis, detected a stimulatory substance whose activity was greatly reduced in the presence of interleukin-1 receptor antagonist protein. Collagenase stimulatory activity present in 28 degrees C culture medium was significantly higher than equal samples from 20 degrees C cultures. These studies provide a molecular correlation between release of cytokines with properties of the metastatic phenotype seen in vivo. They further provide some of the first characterizations of frog MMPs and cytokines, which are likely to be involved in other tissue remodeling events.

Increased interleukin-1 activity in the injured vitamin A-deficient cornea.

Injury to a vitamin A-deficient cornea leads to severe acute inflammation often culminating in ulceration. We report on possible regulatory mechanisms involved in the pathogenesis of corneal inflammation in vitamin A deficiency. Thymocyte comitogenic assay and interleukin (IL)-6 induction in corneal fibroblasts have shown that thermally injured and mechanically abraded vitamin A-deficient rat corneas produce much higher levels of an IL-1-like factor as compared with uninjured or injured, normal control corneas. This was confirmed by antibody capture enzyme immunoassay, which detected high levels of IL-1 alpha and IL-1 beta in injured vitamin A-deficient corneas. To our knowledge this is the first report describing the induction of IL-1 in the vitamin A-deficient cornea by thermal and mechanical injuries. When mechanically injured corneas were screened for chemotactic activity, they were found to contain significantly higher levels of a chemoattractant as compared with similarly injured, normal control corneas. Chemotactic activity [expressed as a percentage of a known chemotactic tripeptide, formyl-methionyl-leucyl-phenylalanine (fMLP), found in medium harvested from vitamin A-deficient corneas] averaged 58.8 +/- 8.9% (SEM) as compared with 12.6 +/- 5.4% in medium conditioned by normal corneas. Checkerboard analysis confirmed that the activity in vitamin A-deficient cornea conditioned medium was chemotactic and not chemokinetic. These results demonstrate a correlation between IL-1 levels and severity of inflammation in the injured vitamin A-deficient rat cornea.

Interleukin-1 regulates the proliferation of leukocytes in human corneal cell-peripheral blood leukocyte cocultures.

We have documented the inability of human corneal epithelial-like cells to suppress proliferation of peripheral blood leukocytes (PBLs) induced by allogeneic PBLs in a mixed leukocyte reaction (MLR). Instead, enhanced proliferation of PBLs, albeit small, was consistently noted as indicated by uptake of radiolabeled thymidine. Maximum proliferation of PBLs was detected when a mixed leukocyte reaction (MLR) was conducted in the presence of corneal cells. High levels of interleukin-1 beta (IL-1 beta) were found during MLR irrespective of the presence of corneal cells. High levels of IL-1 beta correlated well with observed synergistic stimulation of PBL proliferation by corneal cells and stimulating allogeneic PBLs. In PBL-corneal cell cocultures, PBLs produced IL-1 beta; corneal cells contributed large amounts of prostaglandin E2 (PGE2). Although indomethacin completely blocked prostaglandin E2 production, it did not significantly alter the results. Our data show that PBLs and corneal cells can reciprocate each other's presence, and, under appropriate conditions, corneal cells can deliver at least one signal to enhance rather than suppress antigen-driven PBL proliferation. Our data suggest a role for immunoregulatory cytokines and prostanoids such as IL-1 beta and PGE2 in these interactions.

Increased gelatinolytic and caseinolytic activity in the thermally injured, nutritionally compromised rat cornea: detection of a 27-kDa lymphoreticular cell-associated caseinase.

This study assesses the impact of various forms of injury on matrix degrading enzymes in nutritionally compromised rat corneas. In vitamin A-deficient (nutritionally compromised) and normal control corneas, in vivo or ex vivo mild mechanical abrasion did not appreciably alter the activity of either the 65-kDa or the 92-kDa gelatinases. In contrast, after thermal injury, while no appreciable change was detected in activity associated with the 65-kDa gelatinase in either vitamin A-deficient or normal control corneas, 92-kDa gelatinolytic activity was consistently higher in corneas from both groups, although activity associated with nutritionally compromised corneas was much higher. In these corneas, thermal injury also induced the expression of two high molecular weight (approximately 130-kDa and 225-kDa) gelatinases and a 27-kDa caseinase. While gelatinases were totally inactivated by inhibitors of metalloproteinases such as 1,10-phenanthroline and Galardin MPI, the 27-kDa caseinase showed considerable susceptibility to a mixture of serine protease inhibitors (aprotinin, dichloro-isocoumarin and pA-PMSF [(4-amidino-phenyl)-methane-sulphonyl fluoride]. Furthermore, unactivated-lymphoreticular cells from either nutritionally compromised or normal control animals contained a 24- and 27-kDa caseinase, however most of the activity was due to the 24-kDa caseinase. In contrast, glycogen-activated lymphoreticular cells contained a preponderance of the 27-kDa caseinase. Activated-lymphoreticular cells also expressed 92-kDa, 130-kDa and 225-kDa gelatinases. The presence of low molecular weight caseinases in lymphoreticular cells implicates them as the source of these enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vitamin A deficiency on the adhesion of rat corneal epithelium and the basement membrane complex.

PURPOSE: To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency. METHODS: An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen. RESULTS: Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin. CONCLUSIONS: The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea.

Cleavage and activation of corneal matrix metalloproteases by Pseudomonas aeruginosa proteases.

PURPOSE: To examine the effect of Pseudomonas aeruginosa on the expression of corneal matrix metalloproteases and the effect of its proteases on activation of corneal matrix metalloproteases in vitro. METHODS: Rat corneas and human corneal fibroblasts were co-cultivated with two different strains (RPS & 599A) of P. aeruginosa and one strain of Staphylococcus aureus, and the conditioned media were analyzed for proteolytic activity by gelatin and casein zymography. Human corneal fibroblast-conditioned medium was incubated with that from either strain of P. aeruginosa and was analyzed in a similar manner. RESULTS: Normal rat corneas in organ culture produce a 65 kDa gelatinase (inactive matrix metalloprotease-2), whereas thermally injured rat corneas additionally produce gelatinases with molecular masses of 92 kDa (inactive matrix metalloproteases-9) and > 200 kDa. Matrix metalloprotease-2 is also detected in human corneal fibroblast-conditioned medium. Although these matrix metalloproteases are no longer detectable when rat corneas or human corneal fibroblasts are co-cultured with two strains of P. aeruginosa for 48 hr, a 58 kDa gelatinase fragment appears in earlier stages of co-culture. In contrast, S. aureus does not affect matrix metalloprotease-2. The 58 kDa fragment is also evident by incubating human corneal fibroblast-conditioned medium with that from either strain of P. aeruginosa. Conditioned medium from the RPS strain, which produces both elastase and alkaline protease, is more effective in cleaving matrix metalloprotease-2 than that from the 599A strain, which expresses mainly alkaline protease. CONCLUSION: The secreted inactive corneal matrix metalloprotease-2 is activated through limited proteolysis by pseudomonal proteases.

Regulation of mitogen-driven lymphoreticular cell activation by human corneal cells and interleukin-1.

Keratin-positive fibroblast-like epithelial cells (FLE), isolated from human corneo-scleral-conjunctival rims, were shown to inhibit mitogen-driven (concanavalin A) DNA synthesis by murine thymocytes and splenocytes [lymphoreticular cells (LRC)]. The effect exerted by live cells in culture and by their supernatants was caused by factors active across species barriers. Paraformaldehyde-fixed or irradiated cells also suppressed mitogen-induced thymocyte DNA synthesis, but their supernatants manifested no such activity. Interaction between FLE cells and LRC in the presence of the mitogen resulted in suppressed cellular activation as evidenced by significantly lowered tetrazolium salt (MTT) reduction in murine thymocytes and splenocytes, suggesting reduced mitochondrial activity. The suppressive effect was seen with live and paraformaldehyde-fixed FLE cells. There was a good correlation between MTT assays and [3H]thymidine uptake experiments. Suppression of MTT reduction in murine thymocytes and splenocytes by intact FLE cells could be reversed by the addition of interleukin-1 (IL-1). Indomethacin prevented FLE-conditioned medium-induced suppression but failed to relieve suppression by whole FLE cells. Thus, suppression of LRC function by FLE cells and their secretions appeared to operate by different mechanisms. One mechanism related to prostaglandins present in FLE cell-conditioned medium, whereas another mechanism appeared to involve cell-membrane-associated factor(s). The findings not only provide additional information on the capability of corneal cells to regulate lymphoreticular cells but suggest an important role for IL-1 in the regulation of LRC function and corneal inflammation and immunity.

Proteolytic activation of corneal matrix metalloproteinase by Pseudomonas aeruginosa elastase.

Purified Pseudomonas aeruginosa elastase cleaved a 65 kDa gelatinase [inactive proenzyme form of matrix metalloproteinase (MMP-2)] from human corneal fibroblasts into a biologically active fragment with an approximate molecular mass of 58 kDa. However, purified pseudomonal alkaline protease did not cleave MMP-2 appreciably. Since activated MMP-2 is known to degrade native type IV, V and VII collagens, all components of the corneal basement membrane or stroma, our results suggest a new role for pseudomonal elastase in the pathogenesis of corneal infection, inflammation and ulceration.

Cholylglycine measured in serum by RIA and interleukin-1 beta determined by ELISA in differentiating viral hepatitis from chemical liver injury.

Serum bile acids have been shown to serve as useful indicators of liver disease. We have confirmed these findings and added an analysis of interleukin-1 beta (IL-1 beta) profiles to further differentiate viral hepatitis from toxic liver damage associated with exposure to vinyl chloride (VC) or trinitrotoluene (TNT). The frequency of elevated cholylglycine (CG) was 100%, 75%, and 37.5% in viral hepatitis, VC- and TNT-linked liver injury patients, respectively. The mean levels, expressed in micrograms/dL, were 578, 507, 142, and 65 in hepatitis B, hepatitis non-A non-B, VC and TNT liver injury patients, respectively. Thus, the CG test could detect viral hepatitis and, VC liver injury, and (less frequently) liver injury associated with exposure to TNT. The mean level of IL-1 beta in patients with hepatitis type B was 424 pg/mL and hepatitis non A non B was 384 pg/mL compared with a mean of 33-40 pg/mL in those with VC or TNT-linked liver disease. The IL-1 beta detection test proved further to be an important distinguishing parameter as it was 100% positive in patients with viral hepatitis but only 12.5% to 25% positive in patients with VC/TNT-induced liver damage.