Αlpha-thalassemia: A practical overview.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and ß globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.

Compliance and clinical benefit of deferasirox granule and dispersible tablet formulation in pediatric patients with transfusional iron overload: in a randomized, open-label, multicenter, phase II study.

CALYPSO (NCT02435212), a randomized, open-label, multicenter, phase 2 study evaluated the compliance, clinical benefits, and safety of deferasirox granules and dispersible tablets in pediatric patients with iron overload. Iron chelation therapy-naive and iron chelation therapy-pre-treated patients aged 2 to 0.5 mg/mg; 24.5% and 34.2%), upper respiratory tract infection (28.2% and 29.7%), and pyrexia (26.4% and 23.4%). In iron chelation therapy-naive patients, mean compliance and change from baseline in serum ferritin with both deferasirox formulations were not significantly different. The safety profile was comparable between granule and dispersible tablets formulations, and was consistent with the general safety profile of deferasirox.

How I treat non-transfusion-dependent ß-thalassemia.

The intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent ß-thalassemia (NTDT) results in a complex variety of clinical phenotypes that are challenging to diagnose and manage. In this article, we use a clinical framework rooted in pathophysiology to present 4 common scenarios of patients with NTDT. Starting from practical considerations in the diagnosis of NTDT, we delineate our strategy for the longitudinal care of patients who exhibit different constellations of symptoms and complications. We highlight the use of transfusion therapy and novel agents, such as luspatercept, in the patient with anemia-related complications. We also describe our approach to chelation therapy in the patient with iron overload. Although tackling every specific complication of NTDT is beyond the scope of this article, we touch on the management of the various morbidities and multisystem manifestations of the disease.

Effect of natural and synthetic androgen hormone on sex reversal of Nile Tilapia (Oreochromis niloticus).

The present study aimed to produce a monosex population of all male Nile tilapia (Oreochromis spp.) using 17α-methyl testosterone and common carp testes (as a source of natural androgen). Trial was conducted into two consecutive phases, the first was fry (4-5 days old)administration with negative control (without hormone) and positive control (with hormone) feed viz., MT1:60mg/kg, MT2:70mg/kg (17α-MT), carp testis CT1:70% and CT2:80% for 30 days to reverse the sex of male fish and the second phase was nursing the fingerlings for two months on control diet (32% Crude protein).Results revealed a significant growth rate (P<0.05) in the control group where final weight (4.8±0.34ab) and weight gained was recorded as 0.66±0.03ac. In proximate chemical composition of body meat, CT2 treatment showed maximum retention of crude protein, crude fat, and ash whereas dry matter showed maximum retention in MT2 and CT1 treatments. Morphological and histological examination revealed significant difference (p<0.05) in phenotypic males of Nile tilapia fed with the highest percent in MT-treated diet (MT2) of 95±0.58a while MT1, CT2 and CT1 had males of 85±6.0b, 70±5.0b and 65±6.5b, respectively. It was concluded that synthetic androgen (17αMT) was more effective for masculinization but natural androgen scan be an alternative method to produce male tilapia population in an environment-friendly manner as they are inexpensive, eco-friendly, and radially available. These results suggested that synthetic and natural androgen supplementation in the diet plays a significant role in improving growth performance and body composition.

Patient preference for deferasirox film-coated versus dispersible tablet formulation: a sequential-design phase 2 study in patients with thalassemia.

Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet (FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 [95% confidence interval (CI), 0.75-0.89; P < 0.0001]). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.

Thalassaemia-A global view.

The thalassaemias are a group of genetic disorders of haemoglobin which are endemic in the tropics but are now found worldwide due to migration. Basic standard of care therapy includes regular transfusions to maintain a haemoglobin level of around 10 g/dL, together with iron chelation therapy to prevent iron overload. Novel therapies, bone marrow transplantation, and gene therapy are treatment options that are unavailable in many countries with stressed economies. This Wider Perspectives article presents the strategies for management of an adolescent refugee patient with beta thalassaemia, as it would be performed by expert haematologists in six countries: Italy, Lebanon, Oman, the Sudan, Thailand and the United States. The experienced clinicians in each country have adapted their practice according to the resources available, which vary greatly. Even in the current modern era, providing adequate transfusions and chelation is problematic in many countries. On the other hand, ensuring adherence to therapy, particularly during adolescence, is a similar challenge seen in all countries. The concluding section highlights the disparities in available therapies and puts the role of novel therapies into a societal context.

Chromium supplemented carbohydrate diets for Cirrhinus mrigala: effects on body composition, gut enzyme activity and hematological parameters / Dietas com carboidratos suplementados com cromo para Cirrhinus mrigala: efeitos sobre a composição corporal, atividade enzimática intestinal e parâmetros hematológicos

A ninety days nutritional trial was directed to explore the effects of dietary chromium on body composition, gut enzyme activity and physiological status of Cirrhinus mrigala by using G & NG corn. Six experimental diets were prepared by using different levels of chromium chloride hexahydrate (0, 0.2, 0.4 mg/kg, each with G & NG corn). For this experimental trial, 480 fingerlings, irrespective of sex were distributed in six aquariums each with replicate. Results revealed that gelatinized corn along with increasing level of Cr2Cl3.6H2O have a positive impact upon body composition of fish. Hematology was positively correlated with chromium chloride hexahydrate supplementation in gelatinized corn. Amylase gut enzyme also showed significant (P<0.05) increase in group fed with chromium chloride hexahydrate supplemented diet (G corn). However, corn with chromium chloride hexahydrate supplementation did not revealed any significant impact on gut protease enzyme activity. From these results it can be concluded that both chromium chloride hexahydrate and gelatinized corn in fish feed are very beneficial to improve body composition, enzymes activity and physiological health status of fish.

Um ensaio nutricional de 90 dias foi dirigido para explorar os efeitos do cromo dietético na composição corporal, atividade enzimática intestinal e estado fisiológico de Cirrhinus mrigala usando milho G & NG. Seis dietas experimentais foram preparadas usando diferentes níveis de cloreto de cromo hexa-hidratado (0, 0,2, 0,4 mg/kg, cada um com milho G e NG). Para este ensaio experimental, 480 alevinos, independentemente do sexo, foram distribuídos em seis aquários, cada um com réplicas. Os resultados revelaram que o milho gelatinizado, juntamente com o aumento do nível de Cr2Cl3.6H2O, tem um impacto positivo na composição corporal dos peixes. A hematologia foi positivamente correlacionada com a suplementação de cloreto de cromo hexa-hidratado em milho gelatinizado. A enzima amilase intestinal também apresentou aumento significativo (P <0,05) no grupo alimentado com dieta suplementada com cloreto de cromo hexa-hidratado (milho G). No entanto, o milho com suplementação de hexahidrato de cloreto de cromo não revelou nenhum impacto significativo na atividade da enzima protease intestinal. Desses resultados, pode-se concluir que tanto o cloreto de cromo hexa-hidratado quanto o milho gelatinizado na alimentação de peixes são muito benéficos para melhorar a composição corporal, a atividade de enzimas e o estado fisiológico de saúde dos peixes.

Chromium supplemented carbohydrate diets for Cirrhinus mrigala: effects on body composition, gut enzyme activity and hematological parameters

Abstract A ninety days nutritional trial was directed to explore the effects of dietary chromium on body composition, gut enzyme activity and physiological status of Cirrhinus mrigala by using G & NG corn. Six experimental diets were prepared by using different levels of chromium chloride hexahydrate (0, 0.2, 0.4 mg/kg, each with G & NG corn). For this experimental trial, 480 fingerlings, irrespective of sex were distributed in six aquariums each with replicate. Results revealed that gelatinized corn along with increasing level of Cr2Cl3.6H2O have a positive impact upon body composition of fish. Hematology was positively correlated with chromium chloride hexahydrate supplementation in gelatinized corn. Amylase gut enzyme also showed significant (P 0.05) increase in group fed with chromium chloride hexahydrate supplemented diet (G corn). However, corn with chromium chloride hexahydrate supplementation did not revealed any significant impact on gut protease enzyme activity. From these results it can be concluded that both chromium chloride hexahydrate and gelatinized corn in fish feed are very beneficial to improve body composition, enzymes activity and physiological health status of fish.

Resumo Um ensaio nutricional de 90 dias foi dirigido para explorar os efeitos do cromo dietético na composição corporal, atividade enzimática intestinal e estado fisiológico de Cirrhinus mrigala usando milho G & NG. Seis dietas experimentais foram preparadas usando diferentes níveis de cloreto de cromo hexa-hidratado (0, 0,2, 0,4 mg/kg, cada um com milho G e NG). Para este ensaio experimental, 480 alevinos, independentemente do sexo, foram distribuídos em seis aquários, cada um com réplicas. Os resultados revelaram que o milho gelatinizado, juntamente com o aumento do nível de Cr2Cl3.6H2O, tem um impacto positivo na composição corporal dos peixes. A hematologia foi positivamente correlacionada com a suplementação de cloreto de cromo hexa-hidratado em milho gelatinizado. A enzima amilase intestinal também apresentou aumento significativo (P 0,05) no grupo alimentado com dieta suplementada com cloreto de cromo hexa-hidratado (milho G). No entanto, o milho com suplementação de hexahidrato de cloreto de cromo não revelou nenhum impacto significativo na atividade da enzima protease intestinal. Desses resultados, pode-se concluir que tanto o cloreto de cromo hexa-hidratado quanto o milho gelatinizado na alimentação de peixes são muito benéficos para melhorar a composição corporal, a atividade de enzimas e o estado fisiológico de saúde dos peixes.

Bio-efficacy of iron and zinc fortified wheat flour along with bio-assessment of its hepatic and renal toxic potential.

Study was planned to assess the bio-efficiency along with toxicity of iron and zinc fortified whole wheat flour in Sprague dawley albino rats. Whole wheat flour was fortified with different dosage of sodium iron EDTA (NaFeEDTA), ferrous sulphate (FeSO4), zinc oxide (ZnO) and zinc sulphate (ZnSO4). The rats (n=3) in each group were fed on fortified wheat flour for 2 months. Liver biomarkers including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and bilirubin were recorded from serum samples. Increased concentration of ZnSO4 affected the liver biomarkers to be highest among all whereas, bilirubin levels were less than the rats fed on control diet. The above mentioned fortificants have negligible effect on renal biomarkers including creatinine and urea. Moreover, hematological parameters were also checked and reportedly, sodium iron EDTA fed rats presented highest amount of hemoglobin, iron and total iron binding capacity. Highest zinc level was observed in rats fed on whole wheat flour fortified with 60mg/Kg Zinc oxide. Microscopic observation of liver tissue depicted that rats fed on iron and zinc fortified wheat flour have more toxic effects whereas, histopathology presentation of kidney tissue has least toxic impact. It has been concluded that mandatory fortification of wheat flour with iron and zinc may cause increased serum biomarkers along with toxicity of vital organs like liver, hence fraction of wheat flour may be fortified to fulfill the requirements of deprived and vulnerable group.

Antibacterial activity of plant essential oils against indigenously characterized methicillin-resistant Staphylococcus aureus (MRSA).

Plant essential oils were evaluated for antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA). The isolates (n=03) were procured from Institute of Microbiology, UVAS Lahore, Pakistan. After biochemical and 16S rRNA gene-based PCR characterization, accession numbers were retrieved from NCBI i.e. MW344063.1, MW344064.1 and MW344065.1. These isolates exhibited molecular positivity by multiplex PCR for mecA, coa and eta toxin genes. Moreover, these isolates exhibited resistance to cefoxitin, ampicillin, amoxicillin, penicillin, amoxicillin clavulanate, ciprofloxacin, erythromycin and gentamicin. The antibiotic resistant isolates were evaluated for antimicrobial activity of plant essential oils. The highest zone of inhibition (mean ZOI±S.D.) was measured for Cinnamomum verum (22.67±1.52 mm) followed by Eucalyptus globulus (18.67±2.51 mm) and Syzygium aromaticum (12.67±2.51 mm). Lowest mean MIC value (0.33±0.11 mg/mL) was recorded for E. globulus . Eucalyptus globulus was processed for fractionation by column chromatography and n-hexane, chloroform, n-hexane + chloroform and ethyl-acetate fractions were evaluated for antibacterial activity. Lowest mean MIC (10.04±5.80 mg/mL) was recorded for E. globulus n-hexane fraction. Cell survival percentage of BHK21 cell line was 51.7% at 54.87mg/mL concentration of E. globulus n-hexane fraction. Through gas chromatography-mass spectrometry (GC-MS) analysis of n-hexane fraction, benzene was found abundant (29.9%) as active compound. It was concluded that E. globulus n-hexane fraction exhibited significantly promising results against MRSA .

Antiadhesion and antibiofilm potential of Fagonia indica from Cholistan desert against clinical multidrug resistant bacteria / Potencial de antiadesão e antibiofilme de Fagonia indica do deserto do Cholistão contra bactérias multirresistentes clínicas

High resistance to antimicrobials is associated with biofilm formation responsible for infectious microbes to withstand severe conditions. Therefore, new alternatives are necessary as biofilm inhibitors to control infections. In this study, the antimicrobial and antibiofilm activities of Fagonia indica extracts were evaluated against MDR clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica has antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against multidrug resistant (MDR) clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica had antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against MDR isolates. The maximum inhibitory effects of Fagonia indica chloroform extract on biofilm formation was observed on Staphylococcus aureus (71.84%) followed by Klebsiella pneumoniae (70.83%) after 48 hrs showing that inhibition is also time dependent. Our results about bacterial cell protein leakage indicated that MDR isolates treated with chloroform extract of Fagonia indica showed maximum protein leakage of K. pneumoniae (59.14 µg mL-1) followed by S. aureus (56.7 µg mL-1). Cell attachment assays indicated that chloroform extract resulted in a 43.5-53.5% inhibition of cell adherence to a polystyrene surface. Our results revealed that extracts of Fagonia indica significantly inhibited biofilm formation among MDR clinical isolates, therefore, could be applied as antimicrobial agents and cost effective biofilm inhibitor against these MDR isolates.

A alta resistência aos antimicrobianos está associada à formação de biofilme responsável por micróbios infecciosos para suportar condições severas. Portanto, novas alternativas são necessárias como inibidores de biofilme para controlar infecções. Neste estudo, as atividades antimicrobiana e antibiofilme dos extratos de Fagonia indica foram avaliadas contra isolados clínicos MDR. O extrato exibiu seu efeito antibiofilme ao alterar a aderência e a desintegração da parede celular bacteriana. Fagonia indica tem efeito antibacteriano com valores de concentração inibitória mínima (CIM) variando de 125 a 500 µg mL-1, e valor de concentração bactericida mínima (MBC) de 500-3000 µg mL-1 contra isolados clínicos multirresistentes (MDR). O extrato exibiu seu efeito antibiofilme ao alterar a aderência e a desintegração da parede celular bacteriana. Fagonia indica teve efeito antibacteriano com valores de concentração inibitória mínima (CIM) variando de 125 a 500 µg mL-1, e concentração bactericida mínima (MBC) de 500-3000 µg mL-1 contra isolados MDR. Os efeitos inibitórios máximos do extrato de clorofórmio Fagonia indica na formação de biofilme foi observada em Staphylococcus aureus (71,84%), seguido por Klebsiella pneumoniae (70,83%) após 48 horas, mostrando que a inibição também é dependente do tempo. Nossos resultados sobre extravasamento de proteínas de células bacterianas indicaram que isolados MDR tratados com extrato clorofórmico de Fagonia indica apresentaram vazamento máximo de proteínas de K. pneumoniae (59,14 µg mL-1), seguido por S. aureus (56,7 µg mL-1). Ensaios de fixação de células indicaram que o extrato de clorofórmio resultou em uma inibição de 43,5-53,5% da aderência das células a uma superfície de poliestireno. Nossos resultados revelaram que extratos de Fagonia indica inibiram significativamente a formação de biofilme entre isolados clínicos MDR, portanto, poderiam ser aplicados como agentes antimicrobianos e inibidores de biofilme de baixo custo contra esses isolados MDR.

Anticancer Properties of Eugenol: A Review.

Conventional cancer treatments have shown several unfavourable adverse effects, as well as an increase in anticancer drug resistance, which worsens the impending cancer therapy. Thus, the emphasis is currently en route for natural products. There is currently great interest in the natural bioactive components from medicinal plants possessing anticancer characteristics. For example, clove (Syzygium aromaticum L.) (Family Myrtaceae) is a highly prized spice that has been historically utilized as a food preservative and for diverse medical uses. It is reckoned amongst the valued sources of phenolics. It is indigenous to Indonesia but currently is cultivated in various places of the world. Among diverse active components, eugenol, the principal active component of S. aromaticum, has optimistic properties comprising antioxidant, anti-inflammatory, and anticancer actions. Eugenol (4-allyl-2-methoxyphenol) is a musky oil that is mainly obtained from clove. It has long been utilized all over the world as a result of its broad properties like antioxidant, anticancer, anti-inflammatory, and antimicrobial activities. Eugenol continues to pique investigators' interest because of its multidirectional activities, which suggests it could be used in medications to treat different ailments. Anticancer effects of eugenol are accomplished by various mechanisms like inducing cell death, cell cycle arrest, inhibition of migration, metastasis, and angiogenesis on several cancer cell lines. Besides, eugenol might be utilized as an adjunct remedy for patients who are treated with conventional chemotherapy. This combination leads to a boosted effectiveness with decreased toxicity. The present review focuses on the anticancer properties of eugenol to treat several cancer types and their possible mechanisms.

Improving outcomes and quality of life for patients with transfusion-dependent ß-thalassemia: recommendations for best clinical practice and the use of novel treatment strategies.

INTRODUCTION: ß-thalassemia is one of the most common inherited monogenic diseases. Many patients are dependent on a lifetime of red blood cell (RBC) transfusions and iron chelation therapy. Although treatments have a significant impact on quality of life (QoL), life expectancy, and long-term health outcomes have improved in recent decades through safer RBC transfusion practices and better iron chelation strategies. Advances in the understanding of the pathology of ß-thalassemia have led to the development of new treatment options that have the potential to reduce the RBC transfusion burden in patients with transfusion-dependent (TD) ß-thalassemia and improve QoL. AREAS COVERED: This review provides an overview of currently available treatments for patients with TD ß-thalassemia, highlighting QoL issues, and providing an update on current clinical experience plus important practical points for two new treatments available for TD ß-thalassemia: betibeglogene autotemcel (beti-cel) gene therapy and the erythroid maturation agent luspatercept, an activin ligand trap. EXPERT OPINION: Approved therapies, including curative gene therapies and supportive treatments such as luspatercept, have the potential to reduce RBC transfusion burden, and improve clinical outcomes and QoL in patients with TD ß-thalassemia. Cost of treatment is, however, likely to be a significant barrier for payors and patients.

Chromium supplemented carbohydrate diets for Cirrhinus mrigala: effects on body composition, gut enzyme activity and hematological parameters.

A ninety days nutritional trial was directed to explore the effects of dietary chromium on body composition, gut enzyme activity and physiological status of Cirrhinus mrigala by using G & NG corn. Six experimental diets were prepared by using different levels of chromium chloride hexahydrate (0, 0.2, 0.4 mg/kg, each with G & NG corn). For this experimental trial, 480 fingerlings, irrespective of sex were distributed in six aquariums each with replicate. Results revealed that gelatinized corn along with increasing level of Cr2Cl3.6H2O have a positive impact upon body composition of fish. Hematology was positively correlated with chromium chloride hexahydrate supplementation in gelatinized corn. Amylase gut enzyme also showed significant (P<0.05) increase in group fed with chromium chloride hexahydrate supplemented diet (G corn). However, corn with chromium chloride hexahydrate supplementation did not revealed any significant impact on gut protease enzyme activity. From these results it can be concluded that both chromium chloride hexahydrate and gelatinized corn in fish feed are very beneficial to improve body composition, enzymes activity and physiological health status of fish.

Luspatercept for ß-thalassemia: beyond red blood cell transfusions.

INTRODUCTION: Red blood cell transfusions and iron chelation therapy are the cornerstone of treatment for ß-thalassemia, with allogeneic hematopoietic stem cell transplantation and gene therapy offering further disease-management options for eligible patients. With up to 90% of severe cases of ß-thalassemia occurring in resource-constrained countries, and estimates indicating that 22,500 deaths occur annually as a direct consequence of undertransfusion, provision of adequate treatment remains a major issue. AREAS COVERED: In this review, we provide an overview of luspatercept, a first-in-class erythroid maturation agent, and present the available clinical data related to the treatment of ß-thalassemia. EXPERT OPINION: The recent approval of luspatercept offers a new, long-term therapeutic option for adult patients with transfusion-dependent ß-thalassemia to reduce red blood cell transfusion burden, anemia, and iron overload.

2021 update on clinical trials in ß-thalassemia.

The treatment landscape for patients with ß-thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusion-dependent ß-thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost. Patients with non-transfusion-dependent ß-thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in ß-thalassemia, including the α/non-α-globin chain imbalance, ineffective erythropoiesis, and iron dysregulation.

Antiadhesion and antibiofilm potential of Fagonia indica from Cholistan desert against clinical multidrug resistant bacteria.

High resistance to antimicrobials is associated with biofilm formation responsible for infectious microbes to withstand severe conditions. Therefore, new alternatives are necessary as biofilm inhibitors to control infections. In this study, the antimicrobial and antibiofilm activities of Fagonia indica extracts were evaluated against MDR clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica has antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against multidrug resistant (MDR) clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica had antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against MDR isolates. The maximum inhibitory effects of Fagonia indica chloroform extract on biofilm formation was observed on Staphylococcus aureus (71.84%) followed by Klebsiella pneumoniae (70.83%) after 48 hrs showing that inhibition is also time dependent. Our results about bacterial cell protein leakage indicated that MDR isolates treated with chloroform extract of Fagonia indica showed maximum protein leakage of K. pneumoniae (59.14 µg mL-1) followed by S. aureus (56.7 µg mL-1). Cell attachment assays indicated that chloroform extract resulted in a 43.5-53.5% inhibition of cell adherence to a polystyrene surface. Our results revealed that extracts of Fagonia indica significantly inhibited biofilm formation among MDR clinical isolates, therefore, could be applied as antimicrobial agents and cost effective biofilm inhibitor against these MDR isolates.

Platelet-Rich Plasma Ameliorates Monosodium Iodoacetate-Induced Ankle Osteoarthritis in the Rat Model via Suppression of Inflammation and Oxidative Stress.

Until now, there is no treatment that cause complete cure of the chronic inflammatory and degenerative disease, osteoarthritis (OA). Moreover, the underlying mechanisms of OA development and progress are not fully elucidated, and the present pharmacological treatment alternatives are restricted and associated with adverse side effects. Thus, the present study was conducted to evaluate the role of platelet-rich plasma (PRP) in the remedy of OA in the rat model in terms of inflammation, ankle histopathological alterations, and oxidative stress. OA was induced in male Wistar rats by injection of MIA (2 mg)/50 µL isotonic saline in the right ankle joint for two successive days in each rat. After the 2nd MIA injection, the osteoarthritic rats were allocated into two groups such as the MIA group (group 2) and MIA + PRP group (group 3). The MIA + PRP group was treated with PRP (50 µL) by injection into the ankle joint of the right hind limb of each rat at days 14, 21, and 28 after the 2nd injection of MIA. The same equivalent volume of saline, as a substitute of PRP, was injected into the ankle joint of each rat of the normal control group (group 1) and MIA group (group 2) at the same tested periods. Swelling of joint, bodyweight, total leucocytes count (TLC), and morphological as well as histological changes of ankle joints were evaluated. Serum lipid peroxides (LPO), glutathione (GSH), and glutathione S-transferase (GST) levels were examined as biomarkers of oxidative stress. Serum tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and interleukin-4 (IL-4) were investigated by ELISA as biomarkers of inflammation. In addition, magnetic resonance imaging (MRI) was carried out to investigate the soft tissues in joints. The obtained results revealed that PRP reduced LPO and increased GSH and GST levels in osteoarthritic rats. Also, PRP significantly diminished serum TNF-α and IL-17 levels, while it increased IL-4 serum levels in rats with MIA-induced OA. Morphological observations, histological analysis, and MRI revealed a gradual diminishing in joint inflammation and destruction of cartilage in PRP-injected osteoarthritic rats. Based on these results, it can be suggested that PRP has antiarthritic potential in MIA-induced OA, which may be mediated via suppression of inflammation and oxidative stress.