Ethnomedicinal uses of plants for various diseases in the remote areas of Changa Manga Forest, Pakistan / Usos etnomedicinais de plantas para várias doenças nas áreas remotas da Floresta Changa Manga, Paquistão

This study aims at reporting the indigenous knowledge of the medicinal flora from the inhabitants of surroundings of the World's largest artificial planted forest "Changa Manga", Pakistan. Data were collected by direct interviews and group meetings from 81 inhabitants including 32 local healers having information regarding the use of indigenous medicinal plants over a period of one year. Different statistical tools were applied to analyze the data including Frequency citation (FC), Relative frequency citation (RFC), Use Value, Factor of informants consensus and fidelity level. This study reported 73 plant species belonging to 37 plant families and 46 genera. The majority of plant species belong to compositae family. The most commonly used medicinal plants were P. hysterophorus L., P. dactylifera L., S. indicum L, P. harmala L., P. emblica L., and A. indica A.Juss. The greatest number of species was used to cure gastrointestinal disorders. The highest fidelity level (68.18%) was of E. helioscopia to cure gastrointestinal disorders. Maximum fresh uses (17) were reported by C. dactylon (L.) Pars. While the highest number of species reporting fresh uses in similar number was 13. In this study, five novel plants are being reported for the first time in Pakistan for their ethnomedicinal worth. Our data reflect unique usage of the medicinal plants in the study area. The statistical tools used in the study proved useful in pointing the most important and disease category specific plants. High use value plant and the new reported medicinal plants might prove an important source of the isolation of pharmacologically active compounds.

Este estudo tem como objetivo relatar o conhecimento indígena sobre a flora medicinal dos habitantes do entorno da maior floresta artificial plantada do mundo, a Changa Manga, no Paquistão. Os dados foram coletados por meio de entrevistas diretas e reuniões em grupo de 81 habitantes, incluindo 32 curandeiros locais, com informações sobre o uso de plantas medicinais indígenas durante o período de um ano. Diferentes ferramentas estatísticas foram aplicadas para analisar os dados, incluindo citação de frequência (FC), citação de frequência relativa (RFC), valor de uso, fator de consenso dos informantes e nível de fidelidade. Este estudo relatou 73 espécies de plantas pertencentes a 37 famílias de plantas e 46 gêneros. A maioria das espécies de plantas pertence à família Compositae. As plantas medicinais mais utilizadas foram P. hysterophorus L., P. dactylifera L., S. indicum L., P. harmala L., P. emblica L. e A. indica A. Juss. O maior número de espécies foi usado para curar distúrbios gastrointestinais. O maior nível de fidelidade (68,18%) foi de E. helioscopia para cura de distúrbios gastrointestinais. Os usos máximos em fresco (17) foram relatados por C. dactylon (L.) Pars. enquanto o maior número de espécies relatando usos frescos em número semelhante foi de 13. Neste estudo, cinco novas plantas estão sendo relatadas pela primeira vez no Paquistão por seu valor etnomedicinal. Nossos dados refletem o uso exclusivo das plantas medicinais na área de estudo. As ferramentas estatísticas utilizadas no estudo mostraram-se úteis para apontar as plantas mais importantes e específicas da categoria de doença. Plantas de alto valor de uso e as novas plantas medicinais relatadas podem ser uma importante fonte de isolamento de compostos farmacologicamente ativos.

Traditional knowledge about medicinal plant in the remote areas of Wari Tehsil, Dir Upper, Pakistan / Conhecimento tradicional sobre plantas medicinais nas áreas remotas de Wari Tehsil, Dir Upper, Paquistão

Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of [...].

A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das [...].

Traditional knowledge about medicinal plant in the remote areas of Wari Tehsil, Dir Upper, Pakistan

Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitants age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.

Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.

Traditional knowledge about medicinal plant in the remote areas of Wari Tehsil, Dir Upper, Pakistan / Conhecimento tradicional sobre plantas medicinais nas áreas remotas de Wari Tehsil, Dir Upper, Paquistão

Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.

Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados ​​por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.

Ethnomedicinal uses of plants for various diseases in the remote areas of Changa Manga Forest, Pakistan.

This study aims at reporting the indigenous knowledge of the medicinal flora from the inhabitants of surroundings of the World's largest artificial planted forest "Changa Manga", Pakistan. Data were collected by direct interviews and group meetings from 81 inhabitants including 32 local healers having information regarding the use of indigenous medicinal plants over a period of one year. Different statistical tools were applied to analyze the data including Frequency citation (FC), Relative frequency citation (RFC), Use Value, Factor of informants consensus and fidelity level. This study reported 73 plant species belonging to 37 plant families and 46 genera. The majority of plant species belong to compositae family. The most commonly used medicinal plants were P. hysterophorus L., P. dactylifera L., S. indicum L, P. harmala L., P. emblica L., and A. indica A.Juss. The greatest number of species was used to cure gastrointestinal disorders. The highest fidelity level (68.18%) was of E. helioscopia to cure gastrointestinal disorders. Maximum fresh uses (17) were reported by C. dactylon (L.) Pars. While the highest number of species reporting fresh uses in similar number was 13. In this study, five novel plants are being reported for the first time in Pakistan for their ethnomedicinal worth. Our data reflect unique usage of the medicinal plants in the study area. The statistical tools used in the study proved useful in pointing the most important and disease category specific plants. High use value plant and the new reported medicinal plants might prove an important source of the isolation of pharmacologically active compounds.

Traditional knowledge about medicinal plant in the remote areas of Wari Tehsil, Dir Upper, Pakistan.

Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.

Combating COVID-19: The role of drug repurposing and medicinal plants.

BACKGROUND: A novel corona virus-2 disease has spread to 213 countries and territories across the globe. The corona pandemic has claimed more than 548,934 deaths worldwide till the evening of 8th of July 2020 and the number of confirmed cases is increasing at an alarming rate. Therefore, there is an urgent need to find a treatment or a vaccine for COVID-19 at the earliest. The aim of this mini-review is to give an overview of identified repurposed anti-COVID-19 drugs which are currently under clinical trials. METHODS: A thorough literature survey was done to retrieve relevant information using various web based search engines such as Google, Google scholar, and various other electronic research databases such as PubMed, Medline, MeSh etc. The findings of the recently published articles, clinical trials, COVID-19 update by World Health Organization etc., and the opinion of the authors is summarized in this brief review. The antiviral medicinal plants were identified based on their use in Chinese/Indian indigenous systems of medicine, traditional use, published scientific phytochemical studies and/or their effectiveness against upper respiratory infections, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). RESULTS: The disease is just over six months old and effective prophylactic or therapeutic agents are yet to be developed for COVID-19. Thus, in the absence of an effective therapy, scientific community has rationally considered the drug repurposing approach for the development of anti COVID-19 drugs. Various studies and clinical trials involving antimalarial drugs, anti-HIV drugs, anti-hepatitis drugs, anti-parasitic drug, anti-inflammatory drugs, the combination of antimalarial and macrolide antibiotic and few other molecules identified through drug repurposing are currently underway to combat COVID-19. Due emphasis is also given to develop novel corona vaccines for the prophylaxis and to identify drugs for adjunct/supportive therapy. Several medicinal plants along with their major phytochemicals exhibiting antiviral activity are identified for further exploration. It is anticipated that these natural products might also play an important role in combating COVID-19. CONCLUSIONS: Use of drug repurposing strategy to develop anti COVID-19 drugs and exploring antiviral medicinal plants as adjunct or supportive therapy appears to be a viable option. Therefore, it is the need of the hour to work in parallel on different strategies such as genetic engineering, in silico approach, herbal remedies and drug repositioning to achieve the common goal of finding a safe and effective treatment for COVID-19 at the earliest.

Dietary supplementation with glutamine improves gastrointestinal barrier function and promotes compensatory growth of growth-retarded yaks.

The growth retardation of yaks commonly exists on the Tibetan Plateau, and the gastrointestinal barrier function of growth-retarded yaks is disrupted. Glutamine (Gln) is an effective feed additive to improve the gastrointestinal barrier function of animals. This research evaluated the effects of Gln on growth performance, serum permeability parameters, gastrointestinal morphology and barrier function of growth-retarded yaks. Thirty-two male growth-retarded yaks (74.0 ±â€¯6.16 kg of BW and 480 ±â€¯5.50 days of age) were randomly allocated to 4 groups: the negative control (GRY, fed basal ration), Gln1 (fed basal ration and 60 g/d Gln per yak), Gln2 (120 g/d) and Gln3 (180 g/d). Another 8 male growth normal yaks (112 ±â€¯6.11 kg of BW and 480 ±â€¯5.00 days of age) with same breed were used as a positive control (GNY, fed basal ration). The results showed that GRY had lower growth performance and higher (P < 0.05) diamine oxidase, D-lactic acid and lipopolysaccharide concentrations in serum as compared to GNY. Glutamine improved the average daily gain (ADG) of growth-retarded yaks, and the Gln2 group displayed highest ADG. Glutamine supplementation reduced markers of gut permeability in growth-retarded yaks. The GRY and Gln2 groups were selected to study the gastrointestinal barrier function. Growth-retarded yaks fed Gln2 showed higher (P < 0.05) height and surface area of ruminal papillae as compared to GRY. A similar trend of height and surface area in jejunal villus was found between GRY and Gln2 groups. The Gln2 increased (P < 0.05) the concentrations of secretory immunoglobulin A in jejunum and ileum of growth-retarded yaks. The rumen and jejunum of Gln2 yaks exhibited lower (P < 0.05) interleukin-1ß and higher (P < 0.05) interleukin-10 mRNA expressions. Growth-retarded yaks fed Gln2 increased (P < 0.05) the expressions of claudin-1, occludin and zonula occludens-1 in the rumen and jejunum. In conclusion, dietary supplementation with Gln could improve the gastrointestinal barrier function and promote the compensatory growth of growth-retarded yaks.

The role of intra-operative cell salvage in patient blood management for revision hip arthroplasty: a prospective cohort study.

Cell salvage is an important component of blood management in patients undergoing revision hip arthroplasty surgery. However concerns regarding efficacy and patient selection remain. The aims of this study were to describe intra-operative blood loss, cell salvage re-infusion volumes and red blood cell transfusion rates for revision hip procedures and to identify factors associated with the ability to salvage sufficient blood intra-operatively to permit processing and re-infusion. Data were collected from a prospective cohort of 664 consecutive patients undergoing revision hip surgery at a single tertiary centre from 31 March 2015 to 1 April 2018. Indications for revision surgery were aseptic (n = 393 (59%)) fracture (n = 160 (24%)) and infection (n = 111 (17%)). Salvaged blood was processed and re-infused when blood loss exceeded 500 ml. Mean (SD) intra-operative blood loss was 1038 (778) ml across all procedures. Salvaged blood was re-infused in 505 of 664 (76%) patients. Mean (SD) re-infusion volume was 253 (169) ml. In total, 246 of 664 (37%) patients received an allogeneic red blood cell transfusion within 72 h of surgery. Patients undergoing femoral component revision only (OR (95%CI) 0.41 (0.23-0.73)) or acetabular component revision only (0.53 (0.32-0.87)) were less likely to generate sufficient blood salvage volume for re-infusion compared with revision of both components. Compared with aseptic indications, patients undergoing revision surgery for infection (1.87 (1.04-3.36)) or fracture (4.43 (2.30-8.55)) were more likely to generate sufficient blood salvage volume for re-infusion. Our data suggest that cell salvage is efficacious in this population. Cases where the indication is infection or fracture and where both femoral and acetabular components are to be revised should be prioritised.

Superoxide Dismutase in Extender Improves the in vitro Quality and in vivo Fertility of Cryopreserved Water Buffalo (Bubalus bubalis) Spermatozoa.

BACKGROUND: Superoxide dismutase (SOD) as an antioxidant in semen extender may be used for the cryopreservation of buffalo spermatozoa and in vivo fertility. OBJECTIVE: This study was aimed to evaluate the effects of SOD (SOD1, 100 IU/mL; SOD2, 200 IU/mL; SOD3, 300 IU/mL) and control (0.0) in Tris citric acid extender on in vitro quality and in vivo fertility of cryopreserved water buffalo bull spermatozoa. MATERIALS AND METHODS: Semen collection was carried out on a weekly basis (four bulls, three replicates, and n = 24 ejaculates). The conventional freezing of semen loaded straws (0.5 mL) was undertaken by placing them horizontally on a steel rack inside a Styrofoam box for 10 min containing liquid nitrogen (LN2) vapours, and plunging into a liquid nitrogen tank (-196 °C) for storage, followed by thawing at 37 °C for 30 s and analysis by computer-assisted sperm analyzer (CASA) and other assays. RESULTS: At post-dilution, the acrosome integrity (ACR-I, %) was significantly improved (P < 0.05) in extender supplemented with SOD3 as compared to other experimental groups. In addition, DNA integrity (DNA-I, %) was significantly higher (P < 0.05) in SOD1 and SOD3 compared to SOD2 and control. At post-thawing, the mean values of sperm progressive motility (PM, %), average path velocity (VAP, µm/s) and straight line velocity (VSL, µm/s) were significantly higher (P < 0.05) in extender supplemented with SOD3 compared to the control. At post-thawing, mean values of subjective motility (SM, %), plasma membrane integrity (PMI, %) and ACR-I were significantly higher (P < 0.05) in extender supplemented with SOD3 compared to the control. At post-thawing, sperm DNA-I was significantly higher (P < 0.05) in extender supplemented with all SOD doses compared to the control in a dose-dependent manner. The in vivo fertility rate (%) was significantly higher with SOD3 compared to the control (68.2 % vs. 49.5 %). CONCLUSION: The supplementation of SOD3 (300 IU/mL) in Tris citric acid extender improves both in vitro quality and in vivo fertility of buffalo bull spermatozoa.

BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies.

INTRODUCTION: Recombinant factor VIII (rFVIII) products with extended half-lives, such as BAY 94-9027, can potentially maintain higher FVIII levels for longer periods of time, thus providing improved bleeding protection vs standard-acting FVIII products. AIM: To characterize the pharmacokinetic (PK) profile of BAY 94-9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids) clinical trials in adults, adolescents and children with severe haemophilia A METHODS: Patients with severe haemophilia A (FVIII <1%) with >50 FVIII exposure days (EDs) and no history of inhibitors were included in the phase 1 (18-65 years, ≥150 EDs), PROTECT VIII (12-65 years, ≥150 EDs) and PROTECT VIII Kids (<12 years, >50 EDs) trials. PK parameters were assessed following a 25-IU/kg or 60-IU/kg BAY 94-9027 dose in the phase 1 study after the first and repeated infusion, in PROTECT VIII after the first and repeated 60-IU/kg infusion and in PROTECT VIII Kids after a single 60-IU/kg infusion. The chromogenic assay was used to assess FVIII activity. RESULTS: Compared with sucrose-formulated rFVIII, BAY 94-9027 had reduced clearance that resulted in a ~1.4-fold increase in half-life and dose-normalized area under the curve (AUC). The BAY 94-9027 PK profile was comparable after single- and repeated-dose administrations. Dose-proportional increases were observed between 25- and 60-IU/kg administrations. BAY 94-9027 PK characteristics were age dependent, consistent with other FVIII products. CONCLUSIONS: BAY 94-9027 shows an extended half-life and increased AUC vs standard-acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.

Effect of lactic acid bacteria-treated King grass silage on the performance traits and serum metabolites in New Zealand white rabbits (Oryctolagus cuniculus).

This study examined the effects of Lactobacillus plantarum and Pediococcus acidilactici-treated silage of King grass (Pennisetum purpureophoides) on the productive traits and blood biochemistry of New Zealand white (NZW) rabbits. King grass was ensiled without or with L. plantarum (T1), P. acidilactici (T2) and P. acidilactici + L. plantarum (T3). A total of 72 male NZW rabbits (6 weeks) of similar weight and appearance were housed in groups in metallic cages in a completely randomized design. The performance traits, daily feed intake, body weight gain and feed convention ratio were not affected by the silage treatment. Triglyceride and alanine aminotransferase (ALT) concentration was increased (p < .05) in T2 (0.92 mmol/L) compared to the other treatments. The superoxide dismutase (SOD), phosphorous (P) and magnesium (Mg) increased (p < .05) in T1 (658.01 nmol/ml, 5.1 mg/kg and 2.43 mg/kg, respectively) compared to the control and other experimental groups. Cu and Mn decreased (p < .05), while Zn increased (p < .05) in the treated groups compared to the control. The CP decreased (p < .05) in the treatment groups compared to the control. Neutral detergent fibre (NDF) increased (p < .05) in T2 (54.40%) compared to the other treatments. The inoculation of lactic acid bacteria-treated King grass silage supplementation positively affected rabbit performance and improved blood cholesterol profile, antioxidant status and improve nutrients digestibility.

Assessing the impact of perioperative blood transfusions on the survival of adults undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendiceal carcinomatosis.

BACKGROUND AND OBJECTIVES: Perioperative red blood cell transfusions (PBT) may be associated with worse survival. In this study of adults undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), we investigated whether there was an association between PBT and survival. MATERIALS AND METHODS: A retrospective study of adults who had undergone CRS-HIPEC for appendiceal carcinomatosis was conducted. Univariate and multivariate analyses were used to identify factors associated with survival. RESULTS: Of the 270 patients analysed, 170 (63%) received PBT. A PBT was not significantly associated with recurrence-free survival (RFS) (HR = 1·03; 95% CI: 0·7-1·51; P = 0·879) or overall survival (OS) (HR = 0·65; 95% CI: 0·38-1·11; P = 0·116). Higher number of PBT units (≥5) was not associated with worse RFS (P = 0·077) or OS (P = 0·079). Independent predictors of poor survival included as follows: estimated blood loss and high tumour grade for RFS (both P < 0·001), and male gender (P = 0·029) and high tumour grade (P < 0·001) for OS. Higher preoperative haemoglobin was independently associated with better RFS (P = 0·011) and OS (P = 0·006). CONCLUSIONS: In this retrospective study of adults who had undergone CRS-HIPEC for appendiceal carcinomatosis, PBT was not significantly associated with survival.

A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a very common condition affecting more than 10% of the population. While there is no cure, a few drugs have been found to be effective for the relief of symptoms, although most are only effective in a subgroup of patients. We assess and compare the efficacy of a fixed peppermint/caraway-oil-combination (Menthacarin) on symptoms and quality of life (QoL) in patients with FD symptoms consistent with epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). METHODS: In a prospective, double-blind, multicenter trial, 114 outpatients with chronic or recurrent FD were randomized and treated for 4 weeks with the proprietary peppermint- and caraway-oil-preparation Menthacarin or placebo (2×1 capsule/day). Improvement of abdominal pain and discomfort were used as co-primary efficacy measures (scores measured with the validated Nepean Dyspepsia Index). KEY RESULTS: After 2 and 4 weeks, active treatment was superior to placebo in alleviating symptoms consistent with PDS and EPS (P all <.001). After 4 weeks of treatment, pain and discomfort scores improved by 7.6±4.8 and 3.6±2.5 points (full analysis set; mean±SD) for Menthacarin and by 3.4±4.3 and 1.3±2.1 points for placebo, respectively. All secondary efficacy measures showed advantages for Menthacarin. CONCLUSIONS & INFERENCES: Menthacarin is an effective therapy for the relief of pain and discomfort and improvement of disease-specific QoL in patients with FD and significantly improves symptoms consistent with EPS and PDS.

Discovery of anti-microbial and anti-tubercular molecules from Fusarium solani: an endophyte of Glycyrrhiza glabra.

AIMS: Glycyrrhiza glabra is a high-value medicinal plant thriving in biodiversity rich Kashmir Himalaya. The present study was designed to explore the fungal endophytes from G. glabra as a source of bioactive molecules. METHODS AND RESULTS: The extracts prepared from the isolated endophytes were evaluated for anti-microbial activities using broth micro-dilution assay. The endophytic strain coded as A2 exhibiting promising anti-bacterial as well as anti-tuberculosis activity was identified as Fusarium solani by ITS-5.8S ribosomal gene sequencing technique. This strain was subjected to large-scale fermentation followed by isolation of its bioactive compounds using column chromatography. From the results of spectral data analysis and comparison with literature, the molecules were identified as 3,6,9-trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]isochromene-5,10-dione (1), fusarubin (2), 3-O-methylfusarubin (3) and javanicin (4). Compound 1 is reported for the first time from this strain. All the four compounds inhibited the growth of various tested bacterial strains with MIC values in the range of <1 to 256 µg ml-1 . Fusarubin showed good activity against Mycobacterium tuberculosis strain H37Rv with MIC value of 8 µg ml-1 , whereas compounds 1, 3 and 4 exhibited moderate activity with MIC values of 256, 64, 32 µg ml-1 , respectively. CONCLUSIONS: To the best of our knowledge, this is the first study that reports significant anti-tuberculosis potential of bioactive molecules from endophytic F. solani evaluated against the virulent strain of M. tuberculosis. This study sets background towards their synthetic intervention for activity enhancement experiments in anti-microbial drug discovery programme. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to the chemoprofile variation of same endophyte with respect to source plant and ecoregions, further studies are required to explore endophytes of medicinal plants of all unusual biodiversity rich ecoregions for important and or novel bioactive molecules.

Dietary supplementation with glutamine and γ-aminobutyric acid improves growth performance and serum parameters in 22- to 35-day-old broilers exposed to hot environment.

This study was designed using 360 21-day-old chicks to determine the influences of diet supplementation with glutamine (5 g/kg), γ-aminobutyric acid (GABA, 100 mg/kg) or their combinations on performance and serum parameters exposed to cycling high temperatures. From 22 to 35 days, the experimental groups (2 × 2) were subjected to circular heat stress by exposing them to 30-34 °C cycling, while the positive control group was exposed to 23 °C constant. The blood of broilers was collected to detect serum parameters on days 28 and 35. Compared with the positive control group, the cycling high temperature decreased (p < 0.05) the feed consumption, weight gain and serum total protein (TP), glucose, thyroxine (T4), insulin, alkaline phosphatase (ALP), glutamine, GABA and glutamate levels, while increased (p < 0.05) the serum triglyceride (TG), corticosterone (CS), glucagon (GN), creatine kinase (CK), glutamic oxaloacetic transaminase (GOT), nitric oxide synthase (NOS), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) levels during 22-35 days. However, dietary glutamine (5 g/kg) increased (p < 0.05) the feed consumption, weight gain and serum levels of glutamine, TP, insulin and ALP, but decreased (p < 0.05) the serum TG, CK, GOT, NOS and GPT levels. Diet supplemented with GABA also increased (p < 0.05) weight gain and the serum levels of TP, T4, ALP, GABA and glutamine. In addition, the significant interactions (p < 0.05) between glutamine and GABA were found in the feed consumption, weight gain and the serum ALP, CK, LDH, GABA, T3 and T4 levels of heat-stressed chickens. This research indicated that dietary glutamine and GABA improved the antistress ability in performance and serum parameters of broilers under hot environment.

BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial.

INTRODUCTION: BAY 81-8973, a full-length, unmodified, recombinant factor VIII (FVIII) in development for treatment of haemophilia A, has the same primary amino acid sequence as Bayer's sucrose-formulated recombinant FVIII but is produced with more advanced manufacturing technologies. AIM: To demonstrate safety and efficacy of BAY 81-8973 for prophylaxis and treatment of bleeds in previously treated children. METHODS: In this phase III, multicentre, open-label, nonrandomized study, boys aged ≤12 years with severe haemophilia A and ≥50 exposure days (EDs) to FVIII products received prophylaxis with BAY 81-8973 25-50 IU kg(-1) ≥2 times weekly for ≥50 EDs. The efficacy endpoint was annualized number of total bleeds. Adverse events (AEs) and immunogenicity were assessed. RESULTS: Fifty-one patients were treated (age: <6 years, n = 25; 6-<12 years, n = 26) with a 2× per week (43%) or >2× per week (57%) regimen at study start. Median [quartile 1; quartile 3 (Q1; Q3)] annualized number of bleeds for the combined age groups was 1.90 (0; 6.02) for total bleeds, 0 (0; 2.01) for joint bleeds and 0 (0; 0) for spontaneous bleeds. Median (Q1; Q3) annualized number of total bleeds within 48 h of previous prophylaxis infusion was 1.88 (0; 3.97) for children aged <6 years and 0 (0; 1.96) for children aged 6-<12 years. No drug-related serious AEs or inhibitors were reported. CONCLUSIONS: Prophylaxis with BAY 81-8973 using individualized prophylaxis regimens of 2× per week, 3× per week and every-other-day infusions was efficacious in prevention and treatment of bleeds in children with severe haemophilia A. Treatment with BAY 81-8973 was well tolerated.

National Healthcare Delivery Systems Influence Lung Transplant Outcomes for Cystic Fibrosis.

Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post-LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart-lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all-cause mortality. Kaplan-Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68-0.90,p = 0.001 and UK: HR0.63,0.41-0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.

Acupuncture in IVF: A review of current literature.

Women's choice to delay fertility due to various reasons is making subfertility a growing problem and increased use of IVF as a last resort. Despite advances in the technology, IVF success remains low, especially in older women. Hence, many of these women need to undergo several cycles of IVF and are faced with unprecedented anxiety and frustration. In desperation, they resort to anything that might increase the success of their IVF treatment. Acupuncture has gained popularity among the various complementary medicines available and many go privately to have acupuncture while undergoing IVF. Since 1999, in spite of multiple trials and systematic reviews, the beneficial effect of acupuncture in improving the success of IVF remains unproven and debatable. As clinicians, we face the dilemma of what to suggest to our patients when asked about having acupuncture during IVF, given that different meta-analyses have come to different conclusions. Hence, this review is conducted with the aim to summarise the available literature and provide a better insight into this complex and controversial topic.

RTOG 0518: randomized phase III trial to evaluate zoledronic acid for prevention of osteoporosis and associated fractures in prostate cancer patients.

BACKGROUND: RTOG 0518 evaluated the potential benefit of zoledronic acid therapy in preventing bone fractures for patients with high grade and/or locally advanced, non-metastatic prostate adenocarcinoma receiving luteinizing hormone-releasing hormone (LHRH) agonist and radiotherapy (RT). METHODS: Eligible patients with T-scores of the hip (<-1.0, but >-2.5 vs >-1.0) and negative bone scans were prospectively randomized to either zoledronic acid, 4 mg, concurrently with the start of RT and then every six months for a total of 6 infusions (Arm 1) or observation (Arm 2). Vitamin D and calcium supplements were given to all patients. Secondary objectives included quality of life (QOL) and bone mineral density (BMD) changes over a period of three years. RESULTS: Of 109 patients accrued before early closure, 96 were eligible. Median follow-up was 36.3 months for Arm 1 and 34.8 months for Arm 2. Only two patients experienced a bone fracture (one in each arm) resulting in no difference in freedom from any bone fracture (P=0.95), nor in QOL. BMD percent changes from baseline to 36 months were statistically improved with the use of zoledronic acid compared to observation for the lumbar spine (6% vs -5%, P<0.0001), left total hip (1% vs -8%, P=0.0002), and left femoral neck (3% vs -8%, P=0.0007). CONCLUSIONS: For patients with advanced, non-metastatic prostate cancer receiving LHRH agonist and RT, the use of zoledronic acid was associated with statistically improved BMD percent changes. The small number of accrued patients resulted in decreased statistical power to detect any differences in the incidence of bone fractures or QOL.