Volume 27, Issue 2

Despite significant improvements in medical and surgical management, multiple organ dysfunction syndrome (MODS) or multiple organ failure following conditions such as acute pancreatitis, severe sepsis, and traumatic, hemorrhagic, and endotoxin shocks is still accompanied with a high mortality rate. In light of the crucial role of immunologic derangement recently conceptualized in these conditions, ulinastatin, a urinary trypsin inhibitor, is considered as a potentially beneficial immunomodulator drug for MODS. Mechanisms involving protections against tissue organs and endothelial cell and anti-inflammatory effects by ulinastatin are dependent on the inhibition of polymorphonuclear leukocyte (PMN)-derived elastase, tumor necrosis factor α, and other pro-inflammatory cytokines and interleukins (IL-1, IL-6, and IL-8). Ulinastatin also suppresses the activation of PMN cells, macrophages, and platelets. Derived from these properties, ulinastatin has been investigated as a potential clinical therapy for indications including shock and pancreatitis and approved in Japan and China with ongoing clinical trials around the globe. Off-label potential uses of ulinastatin have been reported in preterm labor and hematological, hepatic, renal, and cardiovascular diseases including vasculitis syndromes such as Kawasaki disease.

Background: Phenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain. Methods: Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both ‘Y’ maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin. Results: There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the ‘Y’ maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals. Conclusions: The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.

Background: The present study was designed to investigate the anti-nociceptive activity of a few structurally related trimethoxy flavones (7,2′,3′-TMF, 7,2′,4′-TMF, 7,3′,4′-TMF and 7,5,4′-TMF) and the possible mechanisms involved. Methods: Anti-nociceptive activity was evaluated in mice by employing acetic acid-induced writhing, formalin-induced nociception and hot water tail immersion methods. The involvement of opioid, GABAergic, tryptaminergic, adrenergic and dopaminergic mechanisms and K + ATP channels in the anti-nociceptive activity of trimethoxy flavones was investigated using suitable interacting chemicals. Results: Trimethoxy flavones exhibited a significant and dose-dependent inhibition of acetic acid writhing. The paw-licking response time was reduced both in the early and late phases of formalin nociception in a dose-dependent manner by trimethoxy flavones. A significant increase in tail withdrawal latency time was also observed after trimethoxy flavones treatment. These observations revealed the potential anti-nociceptive action of the investigated trimethoxy flavones. Pretreatment with naloxone and bicuculline significantly attenuated the reduction of abdominal constrictions produced by all the tested trimethoxy flavones indicating a definite role of opioid and GABAergic mechanisms in the anti-nociceptive effect of trimethoxy flavones. The anti-nociceptive action elicited by various trimethoxy flavones was differently modulated by glibenclamide, ondansetron, yohimbine and sulpiride. Conclusions: The investigated trimethoxy flavones exhibited promising anti-nociceptive activity in various nociceptive models, and multiple mechanisms are involved in the anti-nociceptive activity of these compounds.

Background: Flacourtia indica (Burm. f.) Merr. is a medicinal plant indigenous to India and is broadly used worldwide for the treatment of a variety of health ailments. The present study was experimented on hyperlipidemic Charles Foster rats with the aim to explore the possible mechanism responsible for the antidyslipidemic activity of the hydromethanolic extract from F. indica leaves (FIL). Methods: Hyperlipidemia was induced by a single intraperitoneal dose of Triton WR-1339 in Charles Foster rats. The plasma lipid levels were estimated in control and treated groups. The antioxidant potential of F. indica was assessed in both enzymatic and non-enzymatic systems. An acute toxicity study of high-performance liquid chromatography (HPLC)-fingerprinted extract was carried out in Swiss albino mice. Results: The F. indica extract at a dose of 150 mg/kg significantly lowers the plasma level of total cholesterol (17%), triglycerides (13%), and phospholipids (16%) by increasing post-heparin lipolytic activity (19%) and lecithin-cholesterol-acyltransferase activity (20%) in Triton-induced hyperlipidemic rats. In addition, the F. indica extract showed significant in vitro antioxidant and anti-adipogenic activity. HPLC analysis indicates the presence of flavanones and flavones in the extract, and the extract was found to be non-toxic up to a dose of 2000 mg/kg body weight in the acute oral toxicity study. Conclusions: These finding suggest that F. indica holds significant potential in preventing clinical deterioration induced by dyslipidemia along with oxidative stress.

Background: Avocado pear ( Persea americana Mill.) leaves and seeds are used in traditional medicine for the treatment/management of Alzheimer disease (AD); however, information on the mechanism of actions is limited. This study sought to investigate the effect of P. americana leaf and seed aqueous extracts on some enzymes linked with AD (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] activities) and their antioxidant potentials in vitro. Methods: The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of Fe 2+ - and sodium nitroprusside-induced thiobarbiturate reactive species [TBARS] production in rat brain homogenates, radicals [1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and nitric oxide] scavenging and iron [Fe] chelation abilities) were investigated. Phenolic content and phytochemical screening were carried out. Alkaloid profile was also determined using gas chromatography coupled with flame ionization detector (GC-FID). Results: The extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID. Conclusions: The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

Background: Lead induces oxidative stress and alters the antioxidant status of population exposed to high lead levels, i.e. battery manufacturing workers. The aim of this study was to know the current scenario of blood lead (PbB) levels and their effect on the oxidative stress parameter, i.e. serum lipid peroxide (LP), and antioxidant parameters, such as red blood cell (RBC)-superoxide dismutase (SOD), RBC-catalase (CAT), plasma ceruloplasmin (CP), and serum nitrite, of battery manufacturing workers. Methods: Forty-three battery manufacturing workers from Western Maharashtra, India, with ages between 19 and 42 years, were selected as study group and compared with 38 age-matched, healthy male subjects (control group). From both group subjects, 10 mL of blood sample was drawn by puncturing the antecubital vein, and PbB, serum LP, RBC-SOD, RBC-CAT, plasma CP, and serum nitrite were estimated using standard methods. Results: The PbB levels of the battery manufacturing workers were significantly higher (p<0.001, 1050%) as compared with the control subjects. The serum LP levels were significantly increased (p<0.001, 96.86%); all antioxidant status parameters such as RBC-SOD (p<0.001, –26.32%), RBC-CAT (p<0.001, –51.57%), and plasma CP (p<0.001, –35.13%) were significantly decreased; and serum nitrite levels (p<0.001, 154%) were significantly increased in the battery manufacturing workers as compared with the control subjects. Conclusions: Despite modern techniques used to reduce lead exposure in battery manufacturing workers, PbB levels remain high, inducing oxidative stress and altering the antioxidant status of battery manufacturing workers.

Background: Erythrocyte osmotic lysis in deionised glucose media is regulated by glucose influx, cation efflux, and changes in cell volume after water diffusion. Transmembrane fluxes may be affected by varied expression of glucose transporter protein and susceptibility of membrane proteins to glucose-induced glycosylation and oxidation in various physiologic states. Methods: Variations in haemolysis of Sahel goat erythrocytes after incubation in hyposmotic non-ionic glucose media, associated with sex, age, late pregnancy, and lactation, were investigated. Results: The osmotic fragility curve in glucose media was sigmoidal with erythrocytes from goats in late pregnancy (PRE) or lactation (LAC) or from kid (KGT) or middle-aged (MGT) goats. Non-sigmoidal phenotype occurred in yearlings (YGT) and old (OGT) goats. The composite fragility phenotype for males and non-pregnant dry (NPD) females was non-sigmoidal. Erythrocytes with non-sigmoidal curves were more stable than those with sigmoidal curves because of inflectional shift of the curve to the left. Erythrocytes tended to be more fragile with male than female sex, KGT and MGT than YGT and OGT, and LAC and PRE than NPD. Thus, sex, age, pregnancy, and lactation affected the haemolytic pattern of goat erythrocytes in glucose media. Conclusions: The physiologic state of the goat affected the in vitro interaction of glucose with erythrocytes, causing variations in osmotic stability with variants of fragility phenotype. Variations in the effect of high extracellular glucose concentrations on the functions of membrane-associated glucose transporter, aquaporins, and the cation cotransporter were presumed to be relevant in regulating the physical properties of goat erythrocytes under osmotic stress.

Background: The widespread misuse of antibiotics over the past several decades has been regarded as the contributing factor in the development of resistance toward them. Extended spectrum β-lactamases (ESBLs) are enzymes produced by certain bacteria that can make them resistant to certain antibiotics. Early detection of ESBL strains and judicious use of antibiotics and proper implementation of infection control strategies are essential to prevent the spread of this threat in the community. The study aimed at appraising the prevalence, risk factors and antimicrobial susceptibility pattern of ESBL-producing microorganisms. Methods: A prospective observational study was carried out in a tertiary care referral hospital located in Malappuram district of Kerala among inpatients with infection by ESBL-producing bacteria in order to estimate the prevalence, risk factors and their antibiotic susceptibility pattern. Results: Out of the total 1156 patients studied, 118 had confirmed diagnosis on the presence of ESBL-producing microorganisms. Overall, 9.79% of all samples growing Enterobacteriaceae yielded an ESBL producer. Out of the total isolates identified, 66.1% were urinary tract infections, 15.1% were respiratory tract infections, 14.4% were surgical site infections and the remaining constituted blood stream infections. The highest antimicrobial activity against ESBL-producing isolates was observed for meropenem. Conclusions: High prevalence of ESBL-producing organisms is evident in the study setting implicating the necessity to report the ESBL production along with the routine sensitivity reports supplemented with control measures which can assist a clinician in prescribing appropriate antibiotics.

Background : In Nigeria, Cordia sebestena (Boraginaceae), an understudied medicinal plant, is used in traditional medicine for the treatment of gastrointestinal disorders. In this study, we investigated the chemical composition, antibacterial potential, and sub-acute toxicity of C. sebestena leaves. Methods: Ethyl acetate extracts were analyzed using thin layer chromatography (TLC) and Fourier transform infrared (FTIR) spectrophotometry. The antibacterial potential of the extracts was tested against five standard bacteria, namely Bacillus cereus , Bacillus subtilis , Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa . Clinical observations and blood parameters were used to evaluate the possible toxicity of C. sebestena . Results: The TLC profile yielded 39 fractions, which were pooled to nine combined sub-fractions (A–I). The FTIR spectrum of sub-fraction H indicated the presence of aliphatic C-H stretching vibration at 2922 and 2850 cm −1 , C=O stretch at 1734 and 1708 cm −1 , and C=C stretch of aromatics and aliphatics at 1464 and (shoulder) 1618 cm −1 , respectively. The fractions of the C. sebestena ethyl acetate leaf extract showed antibacterial potential across board, but fraction H had the highest antibacterial activity against B. cereus and S. aureus. The study also indicated the relatively low toxicity profile of the ethyl acetate leaf extract of C. sebestena in the liver of rats. Conclusions: The study showed that C. sebestena leaves have strong antibacterial potential and low toxicity, thereby underlying the scientific basis for their folkloric use in the management of microbial infections and its associated complications.

Background: The purpose of this study was to determine if K + is leached from the stratum corneum when sweat is present on the skin’s surface. The results will help address whether sweat [K + ] previously reported in the literature are artifactually elevated as a result of K + leaching. Methods: Twelve (six female, six male) healthy volunteers participated in this study. After thorough skin cleansing and preparation with isopropyl alcohol and high-performance liquid chromatography-grade distilled water, three sites were chosen and a 50 μL drop of artificial sweat was pipetted directly onto the skin. The artificial sweat had a [K + ] of 4 mEq·L –1 , an osmolality of 120 mosm·L –1 , and a pH of 6.0. Immediately following, a clear plastic cover slip (~6 cm 2 ) with a shallow 0.8 cm 2 convex impression in the center was applied over each drop, preventing evaporation. Each sample was allowed to sit on the forearm, under the plastic cover slip, for 10 min. Results: The mean (±SD) [K + ] in ‘artificial’ sweat not exposed to the skin was measured to be 4.2±0.4 mEq·L –1 . After 10 min of exposure to the stratum corneum of the forearm, the artificial sweat had a mean (±SD) [K + ] of 3.9±0.3 mEq·L –1 . There was no significant difference (p>0.05) in the [K + ] between the control artificial sweat and the samples collected after 10 min of exposure to forearm skin. Conclusions: These results do not support the hypothesis that significant K + leaching from the stratum corneum into standing sweat is the cause for the previously reported elevated sweat [K + ].