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1.
Braz. j. biol ; 82: e239219, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153471

RESUMO

Abstract Salmo trutta fario is the most important fish species of family Salmonidae inhibited in cool waters all over the world including the nortern parts of Pakistan. This study was aimed to find out the prey selection and feeding habits of the species. One hundred and eighty five Salmo trutta fario were captured from March 2016 to April 2017. Feeding intensity as represented by a fullness index (FI), changing with various length groups and season. Out of 185 Brown trout 24 fish stomaches were found empty. The most important and common food items of brown trout were Brachycentridae, Blepharocera, Hydropsychidae, ephemerella spp. Kruskal Wallis H-test were applied on feeding intensity groups consisting of three month group. The test statistic for K.W-H-test were (H=8.13 with df =3) had a p-value of 0.043 < (alpha=0.05 indicates favor of the alternative hypothesis of at least one difference among the feeding intensity groups. The linear relationship of N with index of relative importance and %IRI denoted by least square regression line (N = 35.2 + 22.1%IRI), shows that for 22 prey there is 1% change in IRI. The relationship between total length (mm) and fish body weight (gm) is expressed by Pearson correlation coefficient (r = 0.976), showed that total length (mm) and fish body weight (gm.) is highly correlated. Descriptive statistics are used for the stomach fullness, which shows that feeding intensity was recorded higher from March to May. A total of 2289 preys was recorded including the most common were; Trichoptera, Hydropsychidae, Brachycentridae, diptera, blepharocera, ephemerala, chironomida, honey bees, grass hopper, locust, trout egg, trochanter, plant tissue, stones were retrieved from the gut contents of brown trout. According to index of relative importance IRI% four preys represents major components of the diet. The highest IRI% was recorded in Brachycentridae (39.38%), followed by blepharocera (13.23%), Hydropsychidae (10.76%) and ephemerella spp (8.28%). The relationship between IRI and FO is (r =0.556) is moderately correlated with coefficient of determination (r2=0.31). This study will help in the development of an artificial diet for the species for better growth performance in captivity.


Resumo Salmo trutta fario é a espécie de peixe mais importante da família dos salmonídeos, inibida em águas frias em todo o mundo, incluindo as partes do noroeste do Paquistão. Este estudo teve como objetivo conhecer a seleção de presas e os hábitos alimentares da espécie. Cento e oitenta e cinco Salmo trutta fario foram capturados de março de 2016 a abril de 2017. Intensidade de alimentação representada por um índice de plenitude (FI), mudando com vários grupos de comprimento e estação. De 185 trutas, 24 estômagos de peixes foram encontrados vazios. Os itens alimentares mais importantes e comuns da truta marrom foram brachycentridae, blepharocera, hydropsychidae, ephemerellaspp. O teste H de Kruskal Wallis foi aplicado em grupos de intensidade de alimentação consistindo de um grupo de três meses. A estatística de teste para o teste KW-H foi (H = 8,13 com df = 3) teve um valor de p de 0,043 <(alfa = 0,05 indica favor da hipótese alternativa de pelo menos uma diferença entre os grupos de intensidade de alimentação. relação de N com o índice de importância relativa e% IRI denotado pela linha de regressão do mínimo quadrado (N = 35,2 + 22,1% IRI), mostra que para 22 presas há 1% de mudança no IRI. A relação entre comprimento total (mm) e peixes o peso corporal (gm) é expresso pelo coeficiente de correlação de Pearson (r = 0,976), mostrou que o comprimento total (mm) e o peso corporal dos peixes (gm.) são altamente correlacionados. Estatísticas descritivas são usadas para a plenitude do estômago, o que mostra que a intensidade da alimentação foi registrado mais alto de março a maio. Um total de 2.289 presas foi registrado, incluindo os mais comuns foram; trichoptera, hydropsychidae, brachycentridae, diptera, blepharocera, efemérala, chironomida, abelhas, funil de grama, gafanhoto, ovo de truta, trocânter, tecido vegetal, pedras foram retiradas do intestino conteúdo de truta marrom. De acordo com o índice de importância relativa IRI%, quatro presas representam os principais componentes da dieta. O maior IRI% foi registrado em brachycentridae (39,38%), seguido por blepharocera (13,23%), hydropsychidae (10,76%) e ephemerellaspp (8,28%). A relação entre IRI e FO é (r = 0,556) está moderadamente correlacionada com o coeficiente de determinação (r2 = 0,31). Este estudo auxiliará no desenvolvimento de uma dieta artificial para a espécie para melhor desempenho de crescimento em cativeiro.

2.
Physiol Res ; 70(1): 13-26, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33728924

RESUMO

Reactive oxygen species (ROS) such as superoxide (O2-) generated by NAD(P)H oxidases have emerged as important molecules in blood pressure regulation. This study investigated the effect of apocynin and catalase on blood pressure and renal haemodynamic and excretory function in an L-NAME induced hypertension model. Forty Male Wistar-Kyoto (WKY) rats (n=8 per group) were treated with either: vehicle (WKY-C); L-NAME (WKY-L, 15 mg/kg/day in drinking fluid); WKY-L given apocynin to block NAD(P)H oxidase (WKY-LApo, 73 mg/kg/day in drinking water.); WKY-L given catalase to enhance ROS scavenging (WKY-LCat, 10000 U/kg/day i.p.); and WKY-L receiving apocynin plus catalase (WKY-LApoCat) daily for 14 days. L-NAME elevated systolic blood pressure (SBP), 116+/-1 to 181±4 mmHg, reduced creatinine clearance, 1.69+/-0.26 to 0.97+/-0.05 ml/min/kg and fractional sodium excretion, 0.84+/-0.09 to 0.55+/-0.09 % at day 14. Concomitantly, plasma malondialdehyde (MDA) increased six fold, while plasma total superoxide dismutase (T-SOD), plasma nitric oxide (NO) and plasma total antioxidant capacity (T-AOC) were decreased by 60-70 % and Nox 4 mRNA expression was increased 2-fold. Treatment with apocynin and catalase attenuated the increase in SBP and improved renal function, enhanced antioxidative stress capacity and reduced the magnitude of Nox4 mRNAs expression in the L-NAME treated rats. This study demonstrated that apocynin and catalase offset the development of L-NAME induced hypertension, renal dysfunction and reduced oxidative stress status, possibly contributed by a reduction in Nox4 expression during NOS inhibition. These findings would suggest that antioxidant compounds such as apocynin and catalase have potential in treating cardiovascular diseases.

3.
Braz J Biol ; 82: e239219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787749

RESUMO

Salmo trutta fario is the most important fish species of family Salmonidae inhibited in cool waters all over the world including the nortern parts of Pakistan. This study was aimed to find out the prey selection and feeding habits of the species. One hundred and eighty five Salmo trutta fario were captured from March 2016 to April 2017. Feeding intensity as represented by a fullness index (FI), changing with various length groups and season. Out of 185 Brown trout 24 fish stomaches were found empty. The most important and common food items of brown trout were Brachycentridae, Blepharocera, Hydropsychidae, ephemerella spp. Kruskal Wallis H-test were applied on feeding intensity groups consisting of three month group. The test statistic for K.W-H-test were (H=8.13 with df =3) had a p-value of 0.043 < (alpha=0.05 indicates favor of the alternative hypothesis of at least one difference among the feeding intensity groups. The linear relationship of N with index of relative importance and %IRI denoted by least square regression line (N = 35.2 + 22.1%IRI), shows that for 22 prey there is 1% change in IRI. The relationship between total length (mm) and fish body weight (gm) is expressed by Pearson correlation coefficient (r = 0.976), showed that total length (mm) and fish body weight (gm.) is highly correlated. Descriptive statistics are used for the stomach fullness, which shows that feeding intensity was recorded higher from March to May. A total of 2289 preys was recorded including the most common were; Trichoptera, Hydropsychidae, Brachycentridae, diptera, blepharocera, ephemerala, chironomida, honey bees, grass hopper, locust, trout egg, trochanter, plant tissue, stones were retrieved from the gut contents of brown trout. According to index of relative importance IRI% four preys represents major components of the diet. The highest IRI% was recorded in Brachycentridae (39.38%), followed by blepharocera (13.23%), Hydropsychidae (10.76%) and ephemerella spp (8.28%). The relationship between IRI and FO is (r =0.556) is moderately correlated with coefficient of determination (r2=0.31). This study will help in the development of an artificial diet for the species for better growth performance in captivity.


Assuntos
Rios , Truta , Animais , Abelhas , Dieta , Hábitos , Paquistão
4.
Physiol Res ; 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210935

RESUMO

L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5mg/ml p.o.), L-arginine+apocynin (2.5mmol/L p.o.), L-arginine+catalase (10000U/kg/day i.p.) and L-arginine plus apocynin+catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs 91±2mmHg) and heart rate (298±21 vs 254±15b/min), enhanced urinary output (21.5±4.2 vs 32±1.9ml/24h , increased creatinine clearance (1.72±0.56 vs 2.62±0.40ml/min/kg), and fractional sodium excretion (0.88±0.16 vs 1.18±0.16 %), caused proteinuria (28.10±1.93 vs 35.26±1.69mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs 258±5bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by ~51 %, P<0.05) but decreased superoxide dismutase (by ~31 %, P<0.05) and total antioxidant capacity (by~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in states of oxidative stress.

5.
Acta Virol ; 64(3): 331-337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32985210

RESUMO

Every year, the poultry industry experiences significant economic losses due to epidemics of Newcastle disease virus (NDV). Developing new vaccines by identifying and using the immunogenic hemagglutinin-neuraminidase (HN) protein can protect the poultry industry. In the present study, the full-length HN protein was expressed in Escherichia coli (E. coli) BL21 (DE3) cells, purified via affinity chromatography and detected via western blot analysis using His-specific antibodies. The purified HN protein was further evaluated in chickens to study the immune response against NDV. The successful production of HN-specific IgY proved the activity of the purified HN protein. IgY was present in the serum of immunized chickens. However, the immune response was higher in chickens immunized with purified HN protein along with complete and incomplete adjuvants than in chickens immunized with only the HN protein. Keywords: protein; Newcastle disease virus; poultry; infectious diseases; vaccines.

6.
QJM ; 113(5): 347-348, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31800060
7.
Ultrason Sonochem ; 59: 104757, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31479888

RESUMO

The Fe3+ ions were replace with Tb3+ ions as highly paramagnetic rare earth element within the structure of Ni0.4Cu0.2Zn0.4Fe2O4 nano-spinel ferrites (NSFs). The structural, magnetic, spectroscopic and optic properties have been studied in details. All products have been synthesized via ultrasonic approach via Qsonica ultrasonic homogenizer, frequency: 20 kHz and power: 70 W for 60 min. No annealing or calcination process was applied for any product. The microstructural analysis of products has been done via X-ray powder diffractometry (XRD) which presented the cubic spinel structure with nanosized distribution of all. The cubic morphology of all products were confirmed by both HR-TEM and FE-SEM. Optical band gap (Eg) values were assessed by applying %DR (percent diffuse reflectance) analysis and Kubelka-Munk theory. The Tauc schemes showed that Eg values are in a narrow range (1.87-1.98 eV). The quadrupole splitting, line width, hyperfine magnetic field, isomer shift values and cation distribution have been determined from 57Fe Mossbauer analysis. The magnetic properties of various nanoparticles have been obtained from VSM (vibration sample magnetometer) measurements at 10 and 300 K (RT). The magnetic results revealed superparamagnetic and soft ferromagnetic traits at 10 and 300 K, respectively. Ms (saturation magnetization) and Mr (remanence) initially increase with increasing Tb3+ substituting level up to x = 0.06 then diminish for further x values. Hc (coercivity) shows an opposite variation tendency of Ms and Mr. The observed magnetic traits are deeply discussed in relation with the structure, morphology, magnetic moments and cation distributions.

8.
Ultrason Sonochem ; 58: 104638, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31450320

RESUMO

This study expressed the influence of Tm substitution on the structural, optical and magnetic properties of Co-Zn spinel ferrites (Co0.7Zn0.3TmxFe2-xO4 (0.0 ≤ x ≤ 0.04)). The different compositions were synthesized by sonochemical method using Qsonica ultrasonic homogenizer, frequency: 20 kHz and power: 70 W for 60 min. XRD patterns proved the presence of single-phase spinel ferrites with crystallites size in the 8-10 nm range. Cation distribution approved the occupancy of octahedral (B) site by Tm. The morphology and the elements stoichiometry are obtainable through FE-SEM, EDX and elemental mapping. Optical band gap (Eg) values were estimated via DR % (percent diffuse reflectance) investigations and Kubelka-Munk theory. Tauc plots revealed that direct Eg values are ranging between 1.49 and 1.68 eV. The analyses of magnetization versus magnetic field, M(H), were performed. The following magnetic parameters like saturation magnetization Ms, squareness ratio (SQR = Mr/Ms), magnetic moment nB, coercivity Hc and remanence Mr have been evaluated. M(H) curves revealed the superparamagnetic (SP) at RT and ferromagnetic property at 10 K. It was showed that the Tm3+ substitutions significantly affect the magnetic properties of host spinel ferrites. An increasing trend in the Ms, Mr, Hc, and nB values was noticed for lower Tm3+ substitution content.

9.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(6): 435-438, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31204198

RESUMO

OBJECTIVE: Postoperative nasal bleeding is a common complication of septoplasty and may lead to painful procedure of nasal packing to stop bleeding. Since Tranexamic acid (TXA) has been reported to reduce bleeding, the purpose of this study is to investigate the effect of single dose of intravenous TXA on postoperative nasal bleed associated with septoplasty. MATERIALS AND METHODS: This prospective randomized, double-blinded clinical trial consisted of 176 patients aged 18-55 years who underwent septoplasty for symptomatic deviated nasal septum. These participants were randomly divided into 2 groups; 88 patients were given normal saline (Control group) and 88 patients were administered a single shot of intravenous TXA 10mg/kg (TXA group). Operative technique applied was same in all cases. At the end of surgery nasal packs, nasal splints or trans-septal suturing were not done. Nasal bleeding was monitored after surgery and up to 2 weeks postoperatively. RESULTS: Patients receiving TXA showed significantly less postoperative nasal bleeding compared with controls. Extensive bleeding in terms of number of gauze pads used and duration was also higher in placebo with a statistically significant difference (all P=<0.05). Seven patients required nasal packing in control group to stop bleeding as compared to one patient in TXA group. Adverse reactions to TXA were minimal, and these were easily managed conservatively. CONCLUSION: Single intravenous dose of TXA is shown to be effective and safe agent in preventing postoperative nasal bleeding after septoplasty therefore avoiding additional techniques of nasal packing, intranasal splint or trans-septal suturing during surgery.


Assuntos
Epistaxe/tratamento farmacológico , Septo Nasal/cirurgia , Hemorragia Pós-Operatória/tratamento farmacológico , Rinoplastia , Ácido Tranexâmico/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
10.
Ultrason Sonochem ; 57: 203-211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31085087

RESUMO

In this study, Tm3+ ion substituted NiCuZn nanospinel ferrites, Ni0.3Cu0.3Zn0.4TmxFe2-xO4 (0.0 ≤ x ≤ 0.10), have been synthesized sonochemically. The structural, spectroscopic, morphological, optic and magnetic investigation of the samples were done by X-ray powder diffractometry (XRD), Fourier transform infrared spectrophotometry (FT-IR), UV-Vis diffused reflectance (%DR) spectrophotometry, transmission and scanning electron microscopies (TEM and SEM) along with EDX, Vibrating sample magnetometry (VSM), respectively. The purity of prepared products were confirmed via XRD, FT-IR, EDX and elemental mapping analyses. The analyses of magnetization versus M(H) (applied magnetic field) were performed at 300 and 10 K. The following magnetic parameters like Ms (saturation magnetization), SQR = Mr/Ms (squareness ratio), nB(magnetic moment), Hc (coercivity) and Mr (remanence) have been discussed. M(H) loops revealed superparamagnetic property at RT and soft ferromagnetic nature at 10 K. It is showed that the Tm3+ substitutions significantly affect the magnetizations data. A decreasing trend in the Ms, Hc, Mr, and nB values was detected with Tm3+ substitution.

11.
Histol Histopathol ; 34(1): 91-102, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30019745

RESUMO

BACKGROUND: The transparency of the cornea is regulated by the unique organization of collagen fibrils (CFs) which is maintained by proteoglycans (PGs). The interlacing of CF lamellae in the anterior stroma provides the biomechanical properties of the cornea. OBJECTIVE: To investigate the alterations of CFs and PGs in the swollen cornea, with special reference to the anterior stroma by using electron microscopy and 3D ultrastructural tomography. METHOD: Nine healthy normal scleral corneal rings (age from 40 to 65 years) were hydrated individually in deionised water to induce swelling in the cornea. Three of them were hydrated for 2hr whereas the other three were hydrated for 48hr. The remaining three scleral normal corneal rings were used as a control.The corneas were processed for electron microscopy (EM) to study the CFs and PGs. Ultrathin sections were observed using transmission electron microscopy (JOEL 1400) and digital images of CFs, PGs and lamellae were captured using a bottom mounted Quemesa camera and iTEM Soft Imaging System. The software program 'Composer-x64, version 3.4.2.0' was used to construct individual 3D images from 120 digital images taken from -60 to + 60 degree angles. RESULTS: The 3D tomography showed the degeneration of microfibrils within the CFs of the swollen cornea. The CF diameter was significantly reduced and the interfibrillar spacing significantly increased in both the 2hr and 48hr hydrated corneas compared to the normal cornea. Within the hydrated corneas, the CF diameter was smaller and the interfibrillar spacing was increased in the middle and posterior stroma compared to the anterior stroma. The PG area in both the 2hr and the 48hr hydrated cornea was reduced in the anterior stroma, whereas it was increased in middle and posterior stroma compared to the normal cornea. The density of the PGs in both the 2hr and the 48hr samples, was reduced compared to the density of PGs in the normal cornea. CONCLUSION: The CFs, PGs and lamellae had degenerated, caused by swelling. 3D imaging demonstrated that the impairment of the microfibrils and PGs within the CF, is caused by the excessive hydration or swelling in the anterior as well as in the middle and posterior stroma. The lamellae of the anterior stroma which provides the biomechanical strength in the normal cornea, had degenerated in the swollen corneas due to the presence of the damaged CFs and PGs.


Assuntos
Colágeno/ultraestrutura , Substância Própria/ultraestrutura , Proteoglicanas/ultraestrutura , Adulto , Idoso , Edema/patologia , Tomografia com Microscopia Eletrônica , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos
12.
J Nematol ; 50(3): 329-342, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30451418

RESUMO

Conservation agriculture (CA) based on the principles of minimum soil disturbance, crop residue retention, and crop rotation has been the focus of intensive research in recent years. A study was carried out to determine the effects of tillage and fertilizer on the population densities of plant-parasitic nematodes in maize. Three tillage regimes, (i) basin planting, (ii) rip line seeding, and (iii) conventional tillage, were combined with four fertilizer regimes: (i) no-fertilizer, (ii) low fertilizer rate, (iii) medium fertilizer rate, and (iv) high fertilizer rate. The experiment was arranged as a split plot in randomized complete block design, replicated three times with tillage as the main plot factor and fertilizer as the sub-plot factor. The study was conducted on fine-textured Cambisol soils at Chinhoyi University of Technology farm, Zimbabwe, over two cropping seasons between December 2014 and April 2016. Eight plant-parasitic nematode genera were observed belonging to five groups based on their feeding sites: (i) sedentary endoparasites ( Meloidogyne and Rotylenchulus ), (ii) migratory endoparasites ( Pratylenchus ), (iii) semi-endoparasites ( Scutelonema and Helicotylenchus ), (iv) ectoparasites ( Xiphinema and Trichodorus ), and (v) algal, lichen or moss feeders ( Tylenchus ). In both cropping seasons, semi-endoparasitic nematodes were double under rip line seeding and triple under basin planting compared to conventional tillage. Basin planting had higher plant-parasitic nematode richness than rip line seeding. Nematode densities did not have a measurable effect on maize grain yield. Maize grain yield was higher in rip line seeding (37%) and planting basins (52%) than conventional tillage during 2014/15 cropping season. On the other hand, during 2015/16 cropping season, maize grain yield was 78% and 113% higher in rip line seeding and basin planting, respectively, compared to conventional tillage. The results show that under the environmental and edaphic conditions of this specific study site, semi-endoparasitic nematodes were higher under rip line seeding and basin planting compared to conventional tillage. The authors conclude that (i) plant-parasitic nematode genera exhibited differential responses to different tillage systems but were not affected by fertilizer application, and (ii) in the present study, maize grain yield response under different tillage and fertilizer regimes was overall not related to nematode population density and composition.

13.
Contemp Clin Trials ; 71: 124-132, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29908336

RESUMO

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.


Assuntos
Terapia Comportamental/métodos , Buprenorfina/administração & dosagem , Dependência de Heroína , Serviços de Saúde Mental , Metadona/administração & dosagem , Transtornos Relacionados ao Uso de Opioides , Reforço Psicológico , Adulto , Análise por Conglomerados , Uso Indevido de Medicamentos/prevenção & controle , Uso Indevido de Medicamentos/psicologia , Feminino , Dependência de Heroína/psicologia , Dependência de Heroína/terapia , Humanos , Masculino , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/normas , Serviços de Saúde Mental/economia , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/normas , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/psicologia , Transtornos Relacionados ao Uso de Opioides/terapia , Melhoria de Qualidade , Reino Unido
14.
Cryo Letters ; 38(3): 239-249, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28767747

RESUMO

BACKGROUND: There is a possibility to reduce the toxicity of glycerol and osmotic stress of DMSO by lowering their concentrations in freezing extenders. OBJECTIVE: To investigate the effect of glycerol and DMSO in tris-citric acid based extender on post- thaw quality of buffalo (Bubalus bubalis) bull spermatozoa. MATERIALS AND METHODS: Semen was collected from five adult buffalo bulls with artificial vagina. Five aliquots of semen per bull were separated for dilution with the treatment extenders. The first aliquot was diluted at 37C with 6 percent glycerol (T1). The second aliquot was diluted at 37C with extenders containing 4.5 percent glycerol and 1.5 percent DMSO (T2). The third aliquot was diluted with extenders containing 4.5 percent glycerol at 37C and 1.5 percent DMSO at 4С (T3). The fourth aliquot was diluted with extenders containing 1.5 percent DMSO at 37C and 4.5 percent glycerol at 4С (T4). The fifth aliquot was diluted with extender containing 2.5percent DMSO at 37 as well as at 4C (T5). The final concentration of spermatozoa was 50×106/ml in all the treatment groups. Semen was cooled from 37 to 4C in 2 h and equilibration was done at 4 C for 4 h. Later on, packing of cooled semen was undertaken in 0.54 ml French straws and frozen in a programmable cell freezer. RESULTS: At post thawing, treatment groups T1 and T2 yielded significant (P < 0.05) outcome for CASA parameters, longevity, acrosomal integrity, plasma membrane integrity, mitochondrial transmembrane potential and DNA integrity. CONCLUSION: We concluded that by decreasing glycerol concentration (4.5 percent) and combining it with DMSO (1.5 percent) at 37C (T2) in tris-citric acid based extender provided similar results to those observed when glycerol (6 percent) alone is used at 37C (T1) for improving the post-thaw quality of buffalo bull spermatozoa.


Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Preservação do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Animais , Búfalos , Bovinos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Glicerol/farmacologia , Masculino , Motilidade Espermática/efeitos dos fármacos
15.
Blood Cancer J ; 7(5): e565, 2017 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-28548645

RESUMO

Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTKC481S and CXCR4WHIM-like mutations. BTK-mediated signaling was found to be highly attenuated accompanied by a shift in PI3K/AKT and apoptosis regulation-associated genes/proteins. Cytotoxicity studies using the AKT inhibitor, MK2206±ibrutinib, and the Bcl-2-specific inhibitor, venetoclax±ibrutinib, demonstrated synergistic loss of cell viability when either MK22016 or venetoclax were used in combination with ibrutinib. Our findings demonstrate that induction of ibrutinib resistance in WM cells can arise independent of BTKC481S and CXCR4WHIM-like mutations and sustained pressure from ibrutinib appears to activate compensatory AKT signaling as well as reshuffling of Bcl-2 family proteins for maintenance of cell survival. Combination treatment demonstrated greater (and synergistic) antitumor effect and provides rationale for development of therapeutic strategies encompassing venetoclax+ibrutinib or PI3K/AKT inhibitors+ibrutinib in ibrutinib-resistant WM.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Mutação de Sentido Incorreto , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptores CXCR4 , Sulfonamidas/farmacologia , Regulação para Cima/efeitos dos fármacos , Macroglobulinemia de Waldenstrom , Tirosina Quinase da Agamaglobulinemia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Regulação para Cima/genética , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/metabolismo , Macroglobulinemia de Waldenstrom/patologia
16.
Int J Tuberc Lung Dis ; 21(3): 303-308, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28225340

RESUMO

BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan. OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan. METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country. RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates. CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.


Assuntos
Antituberculosos/farmacologia , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/administração & dosagem , Estudos Transversais , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Ofloxacino/farmacologia , Paquistão/epidemiologia , Prevalência , Retratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
18.
Blood Cancer J ; 6(11): e492, 2016 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-27813535

RESUMO

The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.


Assuntos
Azepinas/administração & dosagem , Compostos de Benzilideno/administração & dosagem , Ubiquitina Tiolesterase/antagonistas & inibidores , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Apoptose/efeitos dos fármacos , Bortezomib/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Enzimas Desubiquitinantes/antagonistas & inibidores , Enzimas Desubiquitinantes/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Ubiquitina Tiolesterase/genética , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/patologia
19.
Cell Death Dis ; 7(9): e2367, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27607582

RESUMO

Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.


Assuntos
Autofagia/efeitos dos fármacos , Meios de Cultura Livres de Soro/farmacologia , Peróxido de Hidrogênio/farmacologia , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Autofagia/genética , Biomarcadores/metabolismo , Linhagem Celular , Cloroquina/farmacologia , Técnicas de Cocultura , Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Interleucina-8/biossíntese , Interleucina-8/metabolismo , Macrófagos/citologia , Macrófagos/imunologia , Degeneração Macular/genética , Degeneração Macular/imunologia , Degeneração Macular/patologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/imunologia , Modelos Biológicos , Estresse Oxidativo , Cultura Primária de Células , Epitélio Pigmentado da Retina/imunologia , Epitélio Pigmentado da Retina/patologia , Triancinolona/farmacologia
20.
Ann Hematol ; 95(1): 49-54, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26467917

RESUMO

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma. We report our results of relapsed/refractory NLPHL patients who received high-dose chemotherapy and autogenic stem cell transplantation (HDC auto-SCT). Seventeen NLPHL patients received HDC auto-SCT (1996­2014): male 14 and female 3, with median age at diagnosis of 22 years, at HDC auto-SCT 28 years (15­58 years). At the time of relapse/progression, 13 (76 %) had NLPHL and 4 (24 %) had transformed diffuse large B cell lymphoma. The reason for HDC auto-SCT was refractory NLPHL in 12 patients and relapsed in 5 patients. Salvage chemotherapy was etoposide, methylprednisolone, cisplatinum, and Ara-C (ESHAP); eight patients also received rituximab with ESHAP. HDC was carmustine, etoposide, cytarabine, and melphalan (BEAM). Post-auto-SCT, complete remission was achieved in 14 (82 %), partial remission in 1 (6 %), and progressive disease in 2 (12 %) patients. The median follow-up is 63 months from auto-SCT (6­124 months). Of the nine patients who received only ESHAP, four had post-auto-SCT events versus no event in all eight patients who received rituximab+ESHAP. Kaplan­Meier estimates of 5-year event-free survival for the whole group is 76 %: rituximab+salvage (100 %) versus salvage alone (56 %), P=0.041. Overall survival is 94 %: 100 versus 89 %, respectively, P=not significant (NS). Even in refractory NLPHL patients, long-term disease-free survival is possible after HDC auto-SCT. Post-auto-SCT relapse or progression can still be managed with chemo/chemo+immunotherapy/ radiation. These encouraging results of rituximab in salvage setting should be explored further in a clinical trial setting for this patient population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Adolescente , Adulto , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Transplante Autólogo/métodos , Adulto Jovem
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