(2-Methylbutyryl)shikonin Naturally Occurring Shikonin Derivative Ameliorates the α-MSH-Induced Melanogenesis via ERK1/2 and p38 MAP Kinase-Mediated Down-Regulation of the MITF Transcription Factor.

Cutaneous pigmentation is an important phenotypic trait whose regulation, despite recent advances, has yet to be completely elucidated. Melanogenesis, a physiological process of melanin production, is imperative for organism survival as it provides protection against the environmental insults that majorly involve sunlight-induced skin photodamage. However, immoderate melanin synthesis can cause pigmentation disorders associated with a psychosocial impact. In this study, the hypopigmentation effect of (2-methylbutyryl)shikonin, a natural product present in the root extract of Lithospermum erythrorhizon, and the underlying mechanisms responsible for the inhibition of melanin synthesis in α-MSH-stimulated B16F10 cells and C57BL/6J mice was studied. Non-cytotoxic concentrations of (2-methylbutyryl)shikonin significantly repressed cellular tyrosinase activity and melanin synthesis in both in vitro and in vivo models (C57BL/6J mice). (2-Methylbutyryl)shikonin remarkably abolished the protein expression of MITF, tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2, thereby blocking the production of pigment melanin via modulating the phosphorylation status of MAPK proteins, viz., ERK1/2 and p38. In addition, specific inhibition of ERK1/2 attenuated the inhibitory effects of (2-methylbutyryl)shikonin on melanin synthesis, whereas selective inhibition of p38 augmented the inhibitory effect of BSHK on melanin synthesis. Moreover, topical application of (2-methylbutyryl)shikonin on C57BL/6J mouse tails remarkably induced tail depigmentation. In conclusion, with these findings, we, for the first time, report the hypopigmentation effect of (2-methylbutyryl)shikonin via inhibition of cellular tyrosinase enzyme activity, subsequently ameliorating the melanin production, thereby indicating that (2-methylbutyryl)shikonin is a potential natural therapy for hyperpigmentation disorders.

A clinico-radiological review of chronic non-bacterial osteomyelitis in paediatrics, adolescents, and adults: demystifying a forgotten differential.

Chronic non-bacterial osteomyelitis (CNO), also known as non-bacterial osteitis, is a chronic autoinflammatory disease of unknown aetiology that primarily occurs in the paediatric population, although rare cases of adult-onset disease also exist. CNO has non-specific clinical and radiological presentations, and the affected population often present with bone pain of insidious onset secondary to sterile bony inflammation that can be associated with swelling, focal tenderness, and warmth at the affected sites. The pattern of bony involvement appears to be dependent on the age of onset, with adults frequently having axial skeletal lesions and children and adolescents often being affected in the appendicular skeletal sites. CNO is a diagnosis of exclusion, and imaging is heavily relied on to identify and characterise the bony lesions in addition to exclude diseases that can mimic CNO. Magnetic resonance imaging is often the reference standard with biochemical and histopathological findings being complementary. Although combining imaging methods can be used to facilitate the diagnosis, a single technique could be adequate depending on the clinical picture. Given the relatively rare incidence of CNO, limited awareness of the disease among care providers, and its similarity in clinical and radiological presentation to various bony diseases, there are often long delays in diagnosis, with adults being unfavourably affected compared to paediatrics and adolescents. This review of CNO will describe the condition, overview its clinical presentation, highlight the radiological features, and emphasise clinical pearls that can aid in diagnosis and ruling out the mimics.

Molecular detection of Mycoplasma gallisepticum in different poultry breeds of Abbottabad and Rawalpindi, Pakistan / Detecção molecular de Mycoplasma gallisepticum em diferentes raças de aves de Abbottabad e Rawalpindi, Paquistão

The poultry sector in Pakistan is contributing mainly in bridging gap between demand and supply for protein. Mycoplasma gallisepticum is an emerging bacterium causing serious problems in poultry industry of Pakistan. A cross-sectional study was conducted to evaluate the M. gallisepticum load in poultry populated regions of Pakistan. Total 600 serum and 600 swab samples were collected, 200 from each broiler, layers and breeders poultry in Rawalpindi and Abbottabad districts. Serum samples were analyzed through ELISA for seroprevalence. Swabs were cultured on Frey’s medium followed by PCR and partial mgc2 gene sequencing. Results of seroprevalence of M. gallisepticum showed that layers (75%, n=150) are more positive as compared to breeders (70%, n=140) and broilers (50%, n=100). Typical colonies of the M. gallisepticum were observed in breeder (26.5%), followed by layer (21%) and broilers (9%). A total of 37.1% (n=42) samples were identified positive through PCR out of total 113 cultured based positive samples. A total of six M. gallisepticum isolates of current study showed 98-99 percent similarity with previously reported isolates on the basis of mgc2 gene partial sequencing. The M. gallisepticum was found highly prevalent in different poultry breads. Results of this study would add into basic data and provide a direction for livestock sector to strengthen a control strategy for mycoplasmosis in poultry farms.

O setor avícola do Paquistão está contribuindo principalmente para preencher a lacuna entre a demanda e a oferta de proteína. Mycoplasma gallisepticum é uma bactéria emergente que causa sérios problemas na indústria avícola do Paquistão. Um estudo transversal foi conduzido para avaliar a carga de M. gallisepticum em regiões de avicultura do Paquistão. Um total de 600 amostras de soro e 600 amostras de esfregaço foi coletado, 200 de cada frango de corte, poedeiras e aves reprodutoras nos distritos de Rawalpindi e Abbottabad. Amostras de soro foram analisadas por ELISA para soroprevalência. As zaragatoas foram cultivadas em meio Frey, seguido de PCR e sequenciação parcial do gene mgc2. Os resultados da soroprevalência de M. gallisepticum mostraram que as poedeiras (75%, n = 150) são mais positivas em comparação com matrizes (70%, n = 140) e frangos de corte (50%, n = 100). Colônias típicas de M. gallisepticum foram observadas em reprodutoras (26,5%), seguidas de poedeiras (21%) e frangos de corte (9%). Um total de 37,1% (n = 42) das amostras foi identificado como positivas por PCR de um total de 113 amostras positivas baseadas em cultura. Um total de seis isolados de M. gallisepticum do estudo atual mostrou 98-99% de similaridade com isolados relatados anteriormente com base no sequenciamento parcial do gene mgc2. O M. gallisepticum foi encontrado com alta prevalência em diferentes pães de aves. Os resultados deste estudo acrescentariam dados básicos e forneceriam orientação para o setor pecuário fortalecer uma estratégia de controle da micoplasmose em granjas avícolas.

Molecular detection of Mycoplasma gallisepticum in different poultry breeds of Abbottabad and Rawalpindi, Pakistan

Abstract The poultry sector in Pakistan is contributing mainly in bridging gap between demand and supply for protein. Mycoplasma gallisepticum is an emerging bacterium causing serious problems in poultry industry of Pakistan. A cross-sectional study was conducted to evaluate the M. gallisepticum load in poultry populated regions of Pakistan. Total 600 serum and 600 swab samples were collected, 200 from each broiler, layers and breeders poultry in Rawalpindi and Abbottabad districts. Serum samples were analyzed through ELISA for seroprevalence. Swabs were cultured on Freys medium followed by PCR and partial mgc2 gene sequencing. Results of seroprevalence of M. gallisepticum showed that layers (75%, n=150) are more positive as compared to breeders (70%, n=140) and broilers (50%, n=100). Typical colonies of the M. gallisepticum were observed in breeder (26.5%), followed by layer (21%) and broilers (9%). A total of 37.1% (n=42) samples were identified positive through PCR out of total 113 cultured based positive samples. A total of six M. gallisepticum isolates of current study showed 98-99 percent similarity with previously reported isolates on the basis of mgc2 gene partial sequencing. The M. gallisepticum was found highly prevalent in different poultry breads. Results of this study would add into basic data and provide a direction for livestock sector to strengthen a control strategy for mycoplasmosis in poultry farms.

Resumo O setor avícola do Paquistão está contribuindo principalmente para preencher a lacuna entre a demanda e a oferta de proteína. Mycoplasma gallisepticum é uma bactéria emergente que causa sérios problemas na indústria avícola do Paquistão. Um estudo transversal foi conduzido para avaliar a carga de M. gallisepticum em regiões de avicultura do Paquistão. Um total de 600 amostras de soro e 600 amostras de esfregaço foi coletado, 200 de cada frango de corte, poedeiras e aves reprodutoras nos distritos de Rawalpindi e Abbottabad. Amostras de soro foram analisadas por ELISA para soroprevalência. As zaragatoas foram cultivadas em meio Frey, seguido de PCR e sequenciação parcial do gene mgc2. Os resultados da soroprevalência de M. gallisepticum mostraram que as poedeiras (75%, n = 150) são mais positivas em comparação com matrizes (70%, n = 140) e frangos de corte (50%, n = 100). Colônias típicas de M. gallisepticum foram observadas em reprodutoras (26,5%), seguidas de poedeiras (21%) e frangos de corte (9%). Um total de 37,1% (n = 42) das amostras foi identificado como positivas por PCR de um total de 113 amostras positivas baseadas em cultura. Um total de seis isolados de M. gallisepticum do estudo atual mostrou 98-99% de similaridade com isolados relatados anteriormente com base no sequenciamento parcial do gene mgc2. O M. gallisepticum foi encontrado com alta prevalência em diferentes pães de aves. Os resultados deste estudo acrescentariam dados básicos e forneceriam orientação para o setor pecuário fortalecer uma estratégia de controle da micoplasmose em granjas avícolas.

Molecular detection of Mycoplasma gallisepticum in different poultry breeds of Abbottabad and Rawalpindi, Pakistan / Detecção molecular de Mycoplasma gallisepticum em diferentes raças de aves de Abbottabad e Rawalpindi, Paquistão

Abstract The poultry sector in Pakistan is contributing mainly in bridging gap between demand and supply for protein. Mycoplasma gallisepticum is an emerging bacterium causing serious problems in poultry industry of Pakistan. A cross-sectional study was conducted to evaluate the M. gallisepticum load in poultry populated regions of Pakistan. Total 600 serum and 600 swab samples were collected, 200 from each broiler, layers and breeders poultry in Rawalpindi and Abbottabad districts. Serum samples were analyzed through ELISA for seroprevalence. Swabs were cultured on Frey's medium followed by PCR and partial mgc2 gene sequencing. Results of seroprevalence of M. gallisepticum showed that layers (75%, n=150) are more positive as compared to breeders (70%, n=140) and broilers (50%, n=100). Typical colonies of the M. gallisepticum were observed in breeder (26.5%), followed by layer (21%) and broilers (9%). A total of 37.1% (n=42) samples were identified positive through PCR out of total 113 cultured based positive samples. A total of six M. gallisepticum isolates of current study showed 98-99 percent similarity with previously reported isolates on the basis of mgc2 gene partial sequencing. The M. gallisepticum was found highly prevalent in different poultry breads. Results of this study would add into basic data and provide a direction for livestock sector to strengthen a control strategy for mycoplasmosis in poultry farms.

Resumo O setor avícola do Paquistão está contribuindo principalmente para preencher a lacuna entre a demanda e a oferta de proteína. Mycoplasma gallisepticum é uma bactéria emergente que causa sérios problemas na indústria avícola do Paquistão. Um estudo transversal foi conduzido para avaliar a carga de M. gallisepticum em regiões de avicultura do Paquistão. Um total de 600 amostras de soro e 600 amostras de esfregaço foi coletado, 200 de cada frango de corte, poedeiras e aves reprodutoras nos distritos de Rawalpindi e Abbottabad. Amostras de soro foram analisadas por ELISA para soroprevalência. As zaragatoas foram cultivadas em meio Frey, seguido de PCR e sequenciação parcial do gene mgc2. Os resultados da soroprevalência de M. gallisepticum mostraram que as poedeiras (75%, n = 150) são mais positivas em comparação com matrizes (70%, n = 140) e frangos de corte (50%, n = 100). Colônias típicas de M. gallisepticum foram observadas em reprodutoras (26,5%), seguidas de poedeiras (21%) e frangos de corte (9%). Um total de 37,1% (n = 42) das amostras foi identificado como positivas por PCR de um total de 113 amostras positivas baseadas em cultura. Um total de seis isolados de M. gallisepticum do estudo atual mostrou 98-99% de similaridade com isolados relatados anteriormente com base no sequenciamento parcial do gene mgc2. O M. gallisepticum foi encontrado com alta prevalência em diferentes pães de aves. Os resultados deste estudo acrescentariam dados básicos e forneceriam orientação para o setor pecuário fortalecer uma estratégia de controle da micoplasmose em granjas avícolas.

Food habits of indian crested porcupine (Hystrix indica) (Kerr 1792), in district Bagh, Azad Jammu and Kashmir / Hábitos alimentares do porco-espinho de crista indiano (Hystrix indica) (Kerr 1972) nos distritos de Bagh, Azad Jammu e Caxemira

The Indian Crested Porcupine (Hystrix indica) is classified as an agricultural pest species. It feeds on plants and crops; hence, it is responsible for massive financial losses worldwide. The current study was conducted to assess the diet composition of Indian Crested Porcupine in District Bagh, Azad Jammu and Kashmir (AJ&K). Thus, fecal samples were collected and examined from different sampling sites. Reference slides of the material collected from the study area were prepared for identification of dietary components in fecal pellets. A total of 80 fecal samples were collected and processed. Percent relative frequencies (P.R.F.) were calculated for each plant species recovered from pellets. Data revealed that Indian Crested Porcupine consumed 31 plant species in its diet, among them Zea mays (34.31±7.76) was the most frequently selected species followed by Rumex obtusifolius (15.32±2.57) and Melia azedarach (12.83±4.79). The study revealed that the greatest diversity of (n=20) plant species were consumed in summer season while minimum (n=13) species were used during winter. Among the parts of plants, stem was highly consumed in spring (57.2%) as compared to seed in fall (36.7%) while spikes and leaf were the least recovered parts from the fecal matter. The Berger-Parker diversity index showed highly diversified food (10.92) in the summer time of the year as compared to the autumn season (2.95). This study provides a baseline for the diet preference of this pest in the study area. Based on current findings, a detailed investigation on damage assessment, exploration, habitat use and management of Indian Crested Porcupine in AJ&K has been recommended.

O porco-espinho de crista indiano (Hystrix indica) é classificado como uma espécie de praga agrícola. Alimenta-se de plantas e colheitas; portanto, é responsável por enormes perdas financeiras em todo o mundo. O estudo atual foi realizado para avaliar a composição da dieta do porco-espinho de crista indiano nos distritos de Bagh, Azad Jammu e Caxemira (AJ&K). Assim, amostras fecais foram coletadas e examinadas em diferentes locais de amostragem. Lâminas de referência do material coletado na área de estudo foram preparadas para identificação dos componentes da dieta em pellets fecais. Um total de 80 amostras fecais foi coletado e processado. As frequências relativas percentuais (P.R.F.) foram calculadas para cada espécie de planta recuperada de pelotas. Os dados revelaram que o porco-espinho indiano consumiu 31 espécies de plantas em sua dieta, entre elas Zea mays (34,31 ± 7,76) foi a espécie mais selecionada, seguida por Rumex obtusifolius (15,32 ± 2,57) e Melia azedarach (12,83 ± 4,79). O estudo revelou que a maior diversidade de (n = 20) espécies de plantas foi consumida no verão, enquanto o mínimo (n = 13) espécies foi utilizado durante o inverno. Entre as partes das plantas, o caule foi muito consumido na primavera (57,2%) em relação à semente no outono (36,7%), enquanto a espiga e a folha foram as partes menos recuperadas da matéria fecal., O índice de diversidade de Berger-Parker mostrou alimentos altamente diversificados (10,92) no verão do ano em comparação com o outono (2,95). Este estudo fornece uma linha de base para a preferência alimentar dessa praga na área de estudo. Com base nas descobertas atuais, uma investigação detalhada sobre avaliação de danos, exploração, uso de habitat e gerenciamento de porco-espinho de crista indiano em AJ&K foi recomendada.

Food habits of indian crested porcupine (Hystrix indica) (Kerr 1792), in district Bagh, Azad Jammu and Kashmir

Abstract The Indian Crested Porcupine (Hystrix indica) is classified as an agricultural pest species. It feeds on plants and crops; hence, it is responsible for massive financial losses worldwide. The current study was conducted to assess the diet composition of Indian Crested Porcupine in District Bagh, Azad Jammu and Kashmir (AJ&K). Thus, fecal samples were collected and examined from different sampling sites. Reference slides of the material collected from the study area were prepared for identification of dietary components in fecal pellets. A total of 80 fecal samples were collected and processed. Percent relative frequencies (P.R.F.) were calculated for each plant species recovered from pellets. Data revealed that Indian Crested Porcupine consumed 31 plant species in its diet, among them Zea mays (34.31±7.76) was the most frequently selected species followed by Rumex obtusifolius (15.32±2.57) and Melia azedarach (12.83±4.79). The study revealed that the greatest diversity of (n=20) plant species were consumed in summer season while minimum (n=13) species were used during winter. Among the parts of plants, stem was highly consumed in spring (57.2%) as compared to seed in fall (36.7%) while spikes and leaf were the least recovered parts from the fecal matter. The Berger-Parker diversity index showed highly diversified food (10.92) in the summer time of the year as compared to the autumn season (2.95). This study provides a baseline for the diet preference of this pest in the study area. Based on current findings, a detailed investigation on damage assessment, exploration, habitat use and management of Indian Crested Porcupine in AJ&K has been recommended.

Resumo O porco-espinho de crista indiano (Hystrix indica) é classificado como uma espécie de praga agrícola. Alimenta-se de plantas e colheitas; portanto, é responsável por enormes perdas financeiras em todo o mundo. O estudo atual foi realizado para avaliar a composição da dieta do porco-espinho de crista indiano nos distritos de Bagh, Azad Jammu e Caxemira (AJ&K). Assim, amostras fecais foram coletadas e examinadas em diferentes locais de amostragem. Lâminas de referência do material coletado na área de estudo foram preparadas para identificação dos componentes da dieta em pellets fecais. Um total de 80 amostras fecais foi coletado e processado. As frequências relativas percentuais (P.R.F.) foram calculadas para cada espécie de planta recuperada de pelotas. Os dados revelaram que o porco-espinho indiano consumiu 31 espécies de plantas em sua dieta, entre elas Zea mays (34,31 ± 7,76) foi a espécie mais selecionada, seguida por Rumex obtusifolius (15,32 ± 2,57) e Melia azedarach (12,83 ± 4,79). O estudo revelou que a maior diversidade de (n = 20) espécies de plantas foi consumida no verão, enquanto o mínimo (n = 13) espécies foi utilizado durante o inverno. Entre as partes das plantas, o caule foi muito consumido na primavera (57,2%) em relação à semente no outono (36,7%), enquanto a espiga e a folha foram as partes menos recuperadas da matéria fecal., O índice de diversidade de Berger-Parker mostrou alimentos altamente diversificados (10,92) no verão do ano em comparação com o outono (2,95). Este estudo fornece uma linha de base para a preferência alimentar dessa praga na área de estudo. Com base nas descobertas atuais, uma investigação detalhada sobre avaliação de danos, exploração, uso de habitat e gerenciamento de porco-espinho de crista indiano em AJ&K foi recomendada.

Food habits of indian crested porcupine (Hystrix indica) (Kerr 1792), in district Bagh, Azad Jammu and Kashmir / Hábitos alimentares do porco-espinho de crista indiano (Hystrix indica) (Kerr 1972) nos distritos de Bagh, Azad Jammu e Caxemira

The Indian Crested Porcupine (Hystrix indica) is classified as an agricultural pest species. It feeds on plants and crops; hence, it is responsible for massive financial losses worldwide. The current study was conducted to assess the diet composition of Indian Crested Porcupine in District Bagh, Azad Jammu and Kashmir (AJ&K). Thus, fecal samples were collected and examined from different sampling sites. Reference slides of the material collected from the study area were prepared for identification of dietary components in fecal pellets. A total of 80 fecal samples were collected and processed. Percent relative frequencies (P.R.F.) were calculated for each plant species recovered from pellets. Data revealed that Indian Crested Porcupine consumed 31 plant species in its diet, among them Zea mays (34.31±7.76) was the most frequently selected species followed by Rumex obtusifolius (15.32±2.57) and Melia azedarach (12.83±4.79). The study revealed that the greatest diversity of (n=20) plant species were consumed in summer season while minimum (n=13) species were used during winter. Among the parts of plants, stem was highly consumed in spring (57.2%) as compared to seed in fall (36.7%) while spikes and leaf were the least recovered parts from the fecal matter. The Berger-Parker diversity index showed highly diversified food (10.92) in the summer time of the year as compared to the autumn season (2.95). This study provides a baseline for the diet preference of this pest in the study area. Based on current findings, a detailed investigation on damage assessment, exploration, habitat use and management of Indian Crested Porcupine in AJ&K has been recommended.

O porco-espinho de crista indiano (Hystrix indica) é classificado como uma espécie de praga agrícola. Alimenta-se de plantas e colheitas; portanto, é responsável por enormes perdas financeiras em todo o mundo. O estudo atual foi realizado para avaliar a composição da dieta do porco-espinho de crista indiano nos distritos de Bagh, Azad Jammu e Caxemira (AJ&K). Assim, amostras fecais foram coletadas e examinadas em diferentes locais de amostragem. Lâminas de referência do material coletado na área de estudo foram preparadas para identificação dos componentes da dieta em pellets fecais. Um total de 80 amostras fecais foi coletado e processado. As frequências relativas percentuais (P.R.F.) foram calculadas para cada espécie de planta recuperada de pelotas. Os dados revelaram que o porco-espinho indiano consumiu 31 espécies de plantas em sua dieta, entre elas Zea mays (34,31 ± 7,76) foi a espécie mais selecionada, seguida por Rumex obtusifolius (15,32 ± 2,57) e Melia azedarach (12,83 ± 4,79). O estudo revelou que a maior diversidade de (n = 20) espécies de plantas foi consumida no verão, enquanto o mínimo (n = 13) espécies foi utilizado durante o inverno. Entre as partes das plantas, o caule foi muito consumido na primavera (57,2%) em relação à semente no outono (36,7%), enquanto a espiga e a folha foram as partes menos recuperadas da matéria fecal., O índice de diversidade de Berger-Parker mostrou alimentos altamente diversificados (10,92) no verão do ano em comparação com o outono (2,95). Este estudo fornece uma linha de base para a preferência alimentar dessa praga na área de estudo. Com base nas descobertas atuais, uma investigação detalhada sobre avaliação de danos, exploração, uso de habitat e gerenciamento de porco-espinho de crista indiano em AJ&K foi recomendada.

The work productivity and activity impairment allergic specific (WPAI-AS) questionnaire using mobile technology: the MASK study

No disponible

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2016 revision

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

Pharmaceutical research: paradox, challenge or dilemma?

A great deal of pharmaceutical research is nowadays carried out in developing countries such as Pakistan. Is it, however, beneficial for the country and the participants, often the poorly educated and illiterate? Pharmaceutical research in Pakistan can bring benefits to both patients and country. Promotion of good clinical practice and the development of national guidelines are advocated. Government and industry both have a role to play to maintain the right balance

Transobturator Tape (TOT) for treatment of female stress incontinence : early experience

Objective Evaluation of the transobturator tape (TOT); the newest tension-free technique for the treatment of female stress urinary incontinence (SUI) and its early results with 6 months follow up. Patients and Methods This study was conducted at King Saud Hospital; Saudi Arabia; between September 2002 and March 2004. Fourteen cases with pure SUI were treated with Uratape; a low- elasticity polypropylene tape; according to the technique described by Delorme1;2. Preoperative assessment included full history; urogynecological examination; cough stress test; Q-tip test; cystogram and urodynamic studies. Perioperative cystoscopy was also done. Results No intraoperative complications were recorded. Postoperative complications included transient incisional pain in 2 (14.3); transient voiding difficulty in 5 (35.7) and urgency and frequency withmild pyuria in 3 cases (21.4). Mild groin ecchymosis was seen in 5 cases (35.7). Vaginal wound infection and wound dehiscence with subsequent tape removal occurred in one case only (7.1) Twelve cases (85.7) achieved full continence and one patient (7.1) had minimal leak with extreme stress but was fully satisfied. Conclusion From the promising results of our early experience we conclude that the TOT procedure is a simple; safe; fast and minimally invasive technique for the treatment of SUI in women with few minor complications and a high success rate. Further studies on a larger number of patients will however be needed to confirm these results

Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.

Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.