Unleashing the potential of vanillic acid: A new twist on nature's recipe to fight inflammation and circumvent azole-resistant fungal infections.

Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.

Clerodane Furanoditerpenoids from Tinospora bakis (A.Rich.) Miers (Menispermaceae).

Tinospora bakis (A.Rich.) Miers (Menispermaceae) has traditionally been used to alleviate headaches, rheumatism, mycetoma, and diabetes, among others. Despite its extensive use, the active components of the plant have never been investigated. In this work, a series of furanoditerpenoids (1-18) and five compounds from other classes (19-23) were isolated from T. bakis. Notably, two new compounds were discovered and named: tinobakisin (1) and tinobakiside (10). Their molecular structures were elucidated with NMR, MS, UV, IR, and ECD spectra. Additionally, known compounds (2-9 and 11-23) were corroboratively identified through spectral comparisons with previously reported data, while highlighting and addressing some inaccuracies in the prior literature. Remarkably, compounds 6, 7, 13, and 17 exhibited a superior anti-glycation effect, outperforming established agents like rutin and quercetin in a lab model of protein glycation with glucose. The overall findings suggest that furanoditerpenoids play a crucial role in the antidiabetic properties of T. bakis. This research marks the first comprehensive phytochemical investigation of T. bakis, opening the door for further investigation into furanoditerpenoids and their biological mechanisms.

New anti-inflammatory and non-cytotoxic metabolites of methylstenbolone obtained by microbial transformation.

A synthetic anabolic-androgenic steroid, methylstenbolone (1), was structurally transformed into a series of nine analogues, 2,17α-dimethyl-7α,17ß-dihydroxy-5α-androst-1-en-3-one (2), 2,17α-dimethyl-15ß,17ß-dihydroxy-5α-androst-1-en-3-one (3), 2,17α-dimethyl-6α,9α,17ß-trihydroxy-5α-androst-1-en-3-one (4), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (5), 2-methyl-11ß,17ß-dihydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (6), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3,6-dione (7), 2-methyl-17ß-hydroxy-17α-(hydroxymethyl)-5ß-androst-1-en-3,6-dione (8), 2,17α-dimethyl-7ß,17ß-dihydroxy-5α-androst-1-en-3-one (9), and 2,17α-dimethyl-12ß,17ß-hydroxy-5α-androst-1-en-3,7-dione (10) by fungal cell suspension cultures, Macrophomina phaseolina and Cunninghamella blakesleeana for the first time. Among those, compounds 2-4 and 6-10 were identified as new. Herein, spectral data of metabolite 5 was reported for the first time. Their structures were elucidated by NMR, MS, UV, and IR spectroscopic methods. Substrate 1 (IC50 10.1 ± 0.3 µg/mL) was identified as a potent anti-inflammatory agent against nitric oxide (NO) production. Its transformed products 3 (IC50 as 27.8 ± 1.1 µg/mL) and 9 (26.9 ± 0.4 µg/mL) displayed good inhibition. Compounds 2 (IC50 = 45.9 ± 0.8 µg/mL) and 6 (IC50 = 36.6 ± 1.2 µg/mL) were also active moderately against NO production, in comparison to standard LNMMA (IC50 = 24.2 ± 0.8 µg/mL). Cytotoxicity assay showed 1 was active to cancer cell line MCF7 (IC50 = 12.26 ± 0.35 µg/mL), compared to the standard Doxorubicin having IC50 as 1.25 ± 0.11 µg/mL. However, it is also toxic to human normal cell line (BJ) with IC50 as 8.69 ± 0.02 µg/mL. More importantly, all transformed products are non-cytotoxic on BJ. Therefore, biotransformation can be an efficient approach to reduce the toxicity of methylstenbolone.

Phytochemical Characterizations of Maranthes polyandra (Benth.) Prance.

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.

Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains.

The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16-24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.

Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid.

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5-6 and 8a-8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.

Evaluation of vascular endothelial growth factors A, C and D as indicators of lymphangiogenesis and angiogenesis in invasive and non-invasive urothelial carcinoma bladder.

OBJECTIVE: To study the immunohistochemical expression of vascular endothelial growth factors in urothelial tumours of bladder and its possible association with tumour characteristics and microvessel density. METHODS: The cross-sectional descriptive study was conducted at the Histopathology Department of the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 2011 to December 2012, and comprised cases of non-invasive and invasive urothelial tumours of the bladder. The microvessel density and expression of vascular endothelial growth factors A, C, D were evaluated by immunohistochemistry. Specimens of transurethral bladder biopsies and surgical resection were examined. The cases were classified into non-invasive (stage pTa ) and invasive groups as well as low-grade and high-grade groups. The presence of in-situ component was evaluated in each category. To assess the microvessel density, highly vascularised foci ('hot spots') after immuno-staining with CD34 were quantified for number of vessels per square millimetre and for vascular surface area density. No distinction was made between lymphatic and blood vessels. Vascular endothelial growth factor staining was scored semi-quantitatively. RESULTS: The study examined 100 histopathology specimens, including 90(90%) transurethral bladder biopsies and 10(10%) surgical resection specimens of bladder. There were 45(45%) non-invasive (stage pTa) cases and 55(55%) invasive (stage pT1-4) cases. Besides, there were 43(43%) low-grade (grades 1 and 2) cases, and 57(57%) high-grade (grade 3) cases. Vascular endothelial growth factors A, C and D staining scores showed positive association with stage (p=0.02;p<0.01; p<0.01)and grade (p=0.007;p=0.004; p=0.002) of the tumour. Tumours with in-situ component showed association with number of vessels per square millimetre (p<0.01) and vascular surface area density (p=0.02). CONCLUSIONS: Parameters like vascular endothelial growth factor and microvessel density need to be studied further for selection of cases with potential for targeted therapy.

Injudicious use of laboratory facilities in tertiary care hospitals at Rawalpindi, Pakistan: a cross-sectional descriptive study.

BACKGROUND: In recent years inappropriate and excessive use of clinical laboratory facilities has become a cause of concern and has led to concurrent rise in the laboratory errors and the health care costs. The aim of the study was to find out the frequency of incomplete laboratory request forms, inappropriate test requests at various professional levels and the financial impact of uncollected reports at Armed Forces Institute of Pathology (AFIP) and Combined Military Hospital (CMH) Laboratory Rawalpindi. METHODS: The cross-sectional descriptive study was conducted during a three month period from April to June 2012 at AFIP and CMH Laboratory Rawalpindi. A total of 1000 laboratory request forms were collected and scrutinized for completion from AFIP (n=500) and CMH Rawalpindi laboratory (n=500). 536 request forms of costly/specialized tests from different departments of AFIP were studied to find out the professional level of test request. The total number of tests performed at AFIP during the study period and number of uncollected reports were noted. The financial impact of these uncollected reports was also calculated. Collection of data and sorting were done manually. Patient confidentiality was maintained. Microsoft excel software and SPSS-17 were used for analysis. The study was approved by the Institutional Ethical Review Committee. RESULTS: Out of a total of 1000 forms studied none was completely filled with clinical notes being present in only 2.4% and 13% of forms sent to CMH and AFIP respectively. 62% of the expensive investigations were requested by specialists while 38% were ordered by residents and general practitioners but the percentage of avoidable expensive tests ordered by the general practitioners and residents was significantly higher than the specialists(p<0.001). A total of 9026 (40%) and 5046 (22%) diagnostic test reports were not collected from the Chemical pathology and Hematology departments respectively. Financial impact of uncollected reports from all the departments at AFIP collectively amounted to Pakistani Rupees (PKR) 3338201. CONCLUSION: Processing incomplete laboratory request forms and injudicious use of laboratory facilities leads to incorrect interpretation of laboratory test results affecting outcome of the overall treatment.

Toxic effects of chromium on tannery workers at Sialkot (Pakistan).

Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.

A new sesquiterpene, prosoterpene, from Prosopis africana (Guill. & Perr.) Taub.

A new sesquiterpene (Prosoterpene, 1) and eleven reported compounds (2-12) of several classes, such as flavonoids, alkaloids, phenolic acids, and long-chain alcohols, were isolated from the BuOH extract of Prosopis africana (Guill. & Perr.) Taub. Compounds 2-10 were reported for the first time from this plant. Isomers 11 and 12 were separated for the first time. Extensive spectroscopic techniques and literature comparisons were used to characterise their structures. Furthermore, compounds 3, 5-8, and 10-12 were performed for anti-glycation and cytotoxicity activities. Compound 3 (quercetin-3-O-α-L-rhamnoside) exhibited moderate anti-glycation activity. All tested compounds were non-cytotoxic against MCF-7 (breast cancer), NCI-H460 (lung cancer), Hela (cervical cancer), and BJ (normal human fibroblast) cell lines.

Role of serum-ascites albumin gradient in differential diagnosis of ascites.

BACKGROUND: The classification of ascites as 'exudative' and 'transudative' based on ascitic fluid total protein (AFTP) has been challenged in many clinical conditions like cardiac ascites, patients on prolonged diuretic therapy and malignant ascites because it had poor diagnostic efficacy. These drawbacks have led to the development of another approach to classify ascites, which is based on Serum-Ascites Albumin Gradient (SAAG) to differentiate ascitic fluid into two categories: SAAG > or = 11 g/L in ascites due to portal hypertension and SAAG < 11 g/L in ascites unrelated to portal hypertension. Objective of this study was to compare the diagnostic efficacy of serum/ascites fluid albumin gradient and ascitic fluid total protein in patients having ascites. METHODS: This Cross-sectional comparative study was conducted in the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from 1st Jun 2007 to 30th May 2008. Ninety-three patients were included in the study by non probability convenience sampling. The patient grouped as: (Group I) 73 cases of liver cirrhosis, (Group II) 14 cases of hepatoma and 6 cases of tuberculous ascites. Ascitic fluid specimen and 3 ml blood were obtained for ascitic fluid estimation of ascitic fluid albumin, total proteins and serum albumin. Diagnostic efficacy of SAAG and AFTP was calculated by comparing the results with clinical, ultrasonographic, histopathological findings, ascitic fluid cell count/acid fast bacilli culture and other relevant investigations. RESULTS: Seventy-three cases had liver cirrhosis (group I), 14 cases had hepatoma and 6 cases had tubercular ascites (group II). Age ranged 25-80 years with mean age 56 years. Diagnostic accuracy, Sensitivity, Specificity, Positive predictive value (PPV) and Negative predictive value (NPV) of SAAG were 96%, 97%, 95%, 98.6%, and 90% respectively, whereas those of AFTP were 56%, 53%,70%, 86%, and 29% respectively. CONCLUSION: Differential diagnosis of ascites should be based on SAAG because diagnostic efficacy of SAAG was significantly higher than AFTP in work-up of ascites.

Serum inhibin B as a diagnostic marker of male infertility.

BACKGROUND: Infertility affects about 15% of all couples in the world. Approximately 40% of all infertility cases could be attributed entirely to male factors. Serum inhibin B has emerged as a sensitive marker of male fertility. Analysis of serum inhibin B reflects the relationship between inhibin B, Sertoli cell function and spermatogenesis. METHODS: This validation study was conducted to calculate the sensitivity, specificity, positive and negative predictive value of serum inhibin B in diagnosis of male infertility, using semen analysis as the gold standard. One hundred and sixty men were included in the study, they reported for semen analysis for evaluation of male infertility. Sperm count was done per standard procedure. Serum inhibin B level was determined by ELISA. RESULTS: Serum inhibin B level > or = 80 pg/ml was regarded as a normal response. The serum inhibin B test had 75% sensitivity, 93.1% specificity, 80.5% PPV and 90.7% NPV. CONCLUSION: Serum inhibin B has a positive correlation with sperm counts and could be used for evaluation of male infertility as a non-invasive predictor of spermatogenesis. The sensitivity, specificity and PPV are appropriate for clinical decision making and to avoid unnecessary testicular biopsies.

Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina.

An anabolic-androgenic synthetic steroidal drug, methasterone (1) was transformed by two fungi, Cunninghamella blakesleeana and Macrophimina phaseclina. A total of six transformed products, 6ß,7ß,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (2), 6ß,7α,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (3), 6α,17ß-dihydroxy-2α,17α-dimethyl-5α-androstane-3,7-dione (4), 3ß,6ß,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-7-one (5), 7α,17ß-dihydroxy-2α,17α-dimethyl-5α-androstane-3-one (6), and 6ß,9α,17ß-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (7) were synthesized. Among those, compounds 2-5, and 7 were identified as new transformed products. MS, NMR, and other spectroscopic techniques were performed for the characterization of all compounds. Substrate 1 (IC50 = 23.9 ± 0.2 µg mL-1) showed a remarkable anti-inflammatory activity against nitric oxide (NO) production, in comparison to standard LNMMA (IC50 = 24.2 ± 0.8 µg mL-1). Whereas, its metabolites 2, and 7 showed moderate inhibition with IC50 values of 38.1 ± 0.5 µg mL-1, and 40.2 ± 3.3 µg mL-1, respectively. Moreover, substrate 1 was found to be cytotoxic for the human normal cell line (BJ) with an IC50 of 8.01 ± 0.52 µg mL-1, while metabolites 2-7 were identified as non-cytotoxic. Compounds 1-7 showed no cytotoxicity against MCF-7 (breast cancer), NCI-H460 (lung cancer), and HeLa (cervical cancer) cell lines.

A new steroidal alkaloid from Fritillaria michailovskyi Fomin.

A new steroidal alkaloid, michainine (1), was isolated from Fritillaria michailovskyi Fomin, along with nine known compounds 2-10 of different classes, including ribonucleoside, steroids, and fatty acids, which were isolated for the first time from this plant. Their structures were elucidated through extensive spectroscopic techniques, as well as by comparing the data in the literature. Furthermore, the dichloromethane fraction of F. michailovskyi showed a positive butyrylcholinesterase inhibitory activity, along with non-cytotoxicity against 3T3 cell line.

A new ent-clerodane diterpene from Detarium microcarpum Guill. & Perr. and its protective potential for osteoporosis.

A new clerodane diterpene, named 6α-hydroxy-3,13E-clerodien-15-oic acid (1), together with a known clerodane diterpene (2), four known labdane diterpenes (3-6), a triterpenoid (7), a known steroid (8), and two benzenoid compounds (9 and 10) were isolated from Detarium microcarpum Guill. & Perr. The structures of all obtained compounds were determined by chemical properties and spectroscopic evidence, accompanied by comparisons with data in the literature. Electronic circular dichroism (ECD) was performed for compounds 1-4 to confirm the absolute configuration. Compounds 1-3 and 8-10 were evaluated for the protective effect on osteoblasts. Compound 1 was observed to increase the proliferation of dexamethasone (DEX)-treated MC3T3-E1 cells significantly at 1 µM, which was comparable with the positive control geniposide at 10 µM. The results were further confirmed by flow cytometry analysis. In addition, compound 1 increased the level of alkaline phosphatase (ALP) and mineralization in osteoblasts inhibited by DEX. Moreover, Compound 9 (vanillic acid) showed a pronounced inhibition (IC50 6.5 ± 0.6 µM) on reactive oxygen species (ROS) production, and 10 (4-O-methyl gallic acid) showed a good inhibition with IC50 as 103.3 ± 2.2 µM, compared with the standard drug ibuprofen (IC50 54.2 ± 9.2 µM). Besides, compounds 1-3 and 8-10 were non-cytotoxic against MCF-7, NCI-H460, Hela, and BJ cell lines.

Comparison of serum creatine kinase estimation with short tandem repeats based linkage analysis in carriers and affected children of Duchenne muscular dystrophy.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive lethal, genetic disorder characterised by progressive weakness of skeletal muscles which is untreatable and transmitted to males by carrier females. Advances in laboratory techniques now focus direct mutational analysis as the most reliable and indirect analysis based on Short Tandem Repeats (STR) based linkage analysis as feasible, inexpensive, and efficient method for carrier detection and prenatal diagnosis. The objective of this study was to compare the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of Serum Creatine Kinase (SCK) with Short Tandem Repeats (STR) based linkage analysis in carriers and affected children of Duchenne Muscular Dystrophy. METHODS: The study was carried out from Dec 2006 to Dec 2007 in families having index clinical cases of DMD who were referred from different hospitals for evaluation/workup of DMD. SCK was done as a preliminary investigation in all index cases. The PCR assay with STR based linkage analysis with Intron 44, 45, 49 and 50 of DMD gene were performed in all families. Six families were informative with Intron 44 of DMD gene and one family was non-informative with all four intronic markers of DMD. SCK analyses were done in all the family members and compared with PCR analysis in informative families. SCK was not performed on Chorionic villous sample (CVS) done for prenatal diagnosis of DMD, and CVS and non-informative family members were excluded from the study. RESULTS: In carriers of DMD, the sensitivity and negative predictive value of SCK were 33.3%, and specificity and positive predictive were 100% with diagnostic efficiency of 50%. In affected cases of DMD the sensitivity and negative predictive value of SCK were 100%, and specificity and positive predictive were 91% and 88.8% respectively and diagnostic efficiency of 94.1%. CONCLUSION: The SCK is an excellent screening test for affected cases of DMD. For carrier identification we have to resort on PCR analysis so as to provide safer diagnostic tool for genetic counselling and prenatal diagnosis.

The genus Schefflera: A review of traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Schefflera is the largest genus in the family Araliaceae, which contains 602 known species indigenous to Asia, Africa, and the southwest Pacific region, several of which are used in traditional medicine. AIM OF THE REVIEW: The review discusses current knowledge of the traditional uses, phytochemistry, and biological activities of Schefflera species, to assess the medicinal potential of this genus. MATERIALS AND METHODS: The literature were explored using the keyword "Schefflera" in SciFinder®, Google Scholar®, and PubMed® databases. The taxonomy of all reported plants was authenticated using "The Plant List". Additional data on traditional uses was obtained from secondary references including books and online resources. RESULTS: Fourteen species were documented as traditional medicines in China, India, Vietnam, Thailand, and Indonesia, specifically to manage rheumatism, pain, and trauma. Other species are used in the treatment of liver disorders, skin conditions, respiratory infections, cancer, diarrhea, malaria, paralysis, and many other conditions. The main phytochemical constituents identified were triterpenoids and saponins, with sesquiterpenes, phenylpropanoids, and lignans. Pharmacological properties of extracts and pure isolated compounds included analgesic, anti-inflammatory, anticancer, hypoglycemic, antimicrobial, hepatoprotective, neuroprotective, antimalarial, and antiallergic effects. CONCLUSION: The reported biological activities of Schefflera species support their traditional uses, although the available data, even for medicinal species, was limited. Reports of chemical constituents or biological activities could be found for only about 20 species, but suggest that further investigation of efficacy and safety of the largely unexplored genus Schefflera is necessary.

Amphiphilic desmuramyl peptides for the rational design of new vaccine adjuvants: Synthesis, in vitro modulation of inflammatory response and molecular docking studies.

Nucleotide-binding oligomerization domain 2 (NOD2) is cytosolic surveillance receptor of the innate immune system capable of recognizing the bacterial and viral infections. Muramyl dipeptide (MDP) is the minimal immunoreactive unit of murein. NOD2 perceives MDP as pathogen-associated molecular pattern, thereby triggering an immune response with undesirable side-effects. Beneficial properties of MDP, such as pro-inflammatory characteristics for the rational design of new vaccine adjuvants, can be harnessed by strategically re-designing the molecule. In this work, a new class of amphiphilic desmuramylpeptides (DMPs) were synthesized by replacing the carbohydrate moiety (muramic acid) of the parent molecule with hydrophilic arenes. A lipophilic chain was also introduced at the C-terminus of dipeptide moiety (alanine-isoglutamine), while conserving its L-D configuration. These novel DMPs were found to set off the release of higher levels of tumour necrosis factor alpha (TNF-α) than Murabutide, which is a well-known NOD2 agonist. Molecular docking studies indicate that all these DMPs bind well to NOD2 receptor with similar dock scores (binding energy) through a number of hydrogen bonding and hydrophobic/π interactions with several crucial residues of the receptor. More studies are needed to further assess their immunomodulatory therapeutic potential, as well as the possible involvement of NOD2 activation.

Is procalcitonin better than C-reactive protein for early diagnosis of bacterial pneumonia in children?

Early diagnosis of bacterial pneumonia plays a pivotal role in the management. We evaluated the diagnostic accuracy of procalcitonin (PCT) as compared with C-reactive protein (CRP) for the early diagnosis of bacterial pneumonia in children. In total, 92 children consisting of 46 patients of bacterial pneumonia were admitted in the Military hospital, Rawalpindi, Pakistan and equal number of controls were included. Patient's investigations were carried out at admission. PCT and CRP were analyzed on Vidas analyzer and Immulite 1000, respectively. Out of 46 pneumonia patients, 28 were male and 18 female, with a median age of 4 years. PCT levels were significantly high median (range) of 2.69 ng/ml (0.30-13.00) vs. 0.45 ng/ml (0.10-2.00) in controls. Serum CRP levels were moderately elevated with median (range) 6.5 mg/l (0.30-60) vs. 0.30 mg/l (0.30-5.0) in controls. The area under receiver characteristic curves for PCT and CRP were 0.89 (95% CI=0.83-0.96) and 0.79 (95% CI=0.70-0.88), respectively. In total, 38 patients were diagnosed to have bacterial pneumonia with PCT (sensitivity 83% at cutoff > or = 1 ng/ml) and 26 children with CRP (sensitivity 57% at cutoff > or = 6 mg/L). PCT has better diagnostic accuracy than CRP and can be utilized for early diagnosis of bacterial pneumonia in children.

Lead exposure and its adverse health effects among occupational worker's children.

Lead exposure is an important environmental health problem particularly affecting the children of occupational workers living in the lead-contaminated environment. The objectives of the study were to find out the frequency, potential sources and adverse health effects of elevated blood lead level (BLL) in the children of lead-related occupational workers. It was a comparative cross-sectional study. A total of two hundred forty six children aged 1-6 years, comprising an equal number (n = 123) from lead smelters/battery recycle plant workers living close to the industries at Wah/Gujranwala, Pakistan (lead-exposed group) and those living 30 km away from the industrial area (controls) were included. Demographic and clinical data of each subject was collected. Blood lead analysis was carried out by using kits on the lead analyzer (3010 B ESA, USA). Biochemical tests of renal and hepatic profile were analyzed on Selectra E auto analyzer. The median age of children was 4 years; comprising of 69 boys and 54 girls. The lead-exposed children had significantly high BLLs median (range) 8.1 (1-20.9) microg/dL as compared to controls 6.7 (1-13.3) microg/dL (p 10 microg/dL) in 38 (31%) as compared with 14 (11%) in controls. Hematopoietic, renal, and hepatic functions were significantly impaired in the lead-exposed children. In conclusion, the children of lead-related occupational workers have significantly increased frequency (31%) of lead poisoning. The potential source of lead overexposure in these children may be indirect through father's clothes and contaminated environment at home. Increased lead accumulation adversely affects health of these children.