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1.
Arch Ital Urol Androl ; 96(2): 12335, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38700009

RESUMO

OBJECTIVE: To investigate the correlation between antisperm antibodies (ASAs), pregnancy rates, and the method of conception following vasectomy reversal. This is particularly relevant as patients undergoing vasectomy reversal often express concerns about the potential inhibitory effects of ASAs on achieving pregnancy. Additionally, the American Urological Association guidelines for vasectomy emphasize the need for further research to address this question. PATIENT AND METHODS: We conducted a retrospective analysis involving chart reviews and phone interviews with individuals who underwent vasectomy reversal at our institution between May 2015 and April 2023. Patients who underwent vasectomy reversal for reasons other than fertility, as well as those lacking postoperative semen analysis with ASA data, were excluded. We classified patients based on low (below 50%) or high (50% or above) ASA levels determined by their initial postoperative semen analysis. The primary outcome measured was the pregnancy rate, including details on the method of conception. RESULTS: A total of 145 patients were subjected to chart review. The median age at the time of surgery was 43 years, with a median obstruction interval of 7.7 years. The median age of their partners was 29 years. The majority (80%) of patients underwent bilateral vasovasostomy. Among them, 60 patients (41.4%) exhibited low (< 50%) ASA levels, while 85 (58.6%) had high (≥ 50%) ASA levels. Follow-up phone interviews were completed by 48 patients. Among them, the 19 men with low ASA levels, 13 (68.4%) achieved pregnancy, with 6 (31.6%) experiencing spontaneous conception. For the 29 men with high ASA levels, 21 (72.4%) achieved pregnancy, including 11 (38%) through spontaneous conception. The p-value from Fisher's exact test was 0.2. CONCLUSIONS: Our findings suggest that ASA levels do not show a significant association with either the pregnancy rate or the method of conception following vasectomy reversal.


Assuntos
Taxa de Gravidez , Vasovasostomia , Humanos , Gravidez , Estudos Retrospectivos , Feminino , Adulto , Masculino , Vasovasostomia/métodos , Espermatozoides/imunologia , Pessoa de Meia-Idade , Autoanticorpos/imunologia , Análise do Sêmen
2.
Sci Adv ; 10(9): eadk3074, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416824

RESUMO

Cancer cells program fibroblasts into cancer associated fibroblasts (CAFs) in a two-step manner. First, cancer cells secrete exosomes to program quiescent fibroblasts into activated CAFs. Second, cancer cells maintain the CAF phenotype via activation of signal transduction pathways. We rationalized that inhibiting this two-step process can normalize CAFs into quiescent fibroblasts and augment the efficacy of immunotherapy. We show that cancer cell-targeted nanoliposomes that inhibit sequential steps of exosome biogenesis and release from lung cancer cells block the differentiation of lung fibroblasts into CAFs. In parallel, we demonstrate that CAF-targeted nanoliposomes that block two distinct nodes in fibroblast growth factor receptor (FGFR)-Wnt/ß-catenin signaling pathway can reverse activate CAFs into quiescent fibroblasts. Co-administration of both nanoliposomes significantly improves the infiltration of cytotoxic T cells and enhances the antitumor efficacy of αPD-L1 in immunocompetent lung cancer-bearing mice. Simultaneously blocking the tumoral exosome-mediated activation of fibroblasts and FGFR-Wnt/ß-catenin signaling constitutes a promising approach to augment immunotherapy.


Assuntos
Exossomos , Neoplasias Pulmonares , Animais , Camundongos , Exossomos/metabolismo , Proliferação de Células/genética , Fibroblastos/metabolismo , Neoplasias Pulmonares/genética , Fenótipo , Imunoterapia , Linhagem Celular Tumoral
3.
Sci Rep ; 13(1): 20465, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993582

RESUMO

The present study applies the improved stratigraphic modified Lorenz (ISML) technique to divide the Matulla Formation in Muzhil Oil Field in the Gulf of Suez into some hydraulic flow units (HFUs) and to check the flow efficiency contribution of each hydraulic flow unit (HFU) to the total bulk flow capacity of the reservoir in 3 wells (Muzhil-4, 7, and 8). The output of the ISML plot is applied in integration with the vertical plot of the porosity (∅), permeability (k), and effective pore radius (R35) against depth to measure the efficiency of each HFU contribution to the total flow capacity of the Matulla reservoir, and to delineate the main attributor to the flow capacity. It is indicated that the Matulla sandstone reservoirs can be subdivided into 7 HFUs to the NW of the field, while it is subdivided into four and five HFUs in the center and to the SE of the field; i.e., its heterogeneity increases to the NW at Muzhil-7 well. On the other side, the best reservoir quality is assigned to the southeast at Muzhil-4 well (av. ∅ = 20.8%, av. k = 596.6 md, and R35 = 12.1 µm). The efficiency of the obtained HFUs was estimated and described both mathematically and graphically. Also, the measured porosity and permeability values indicate relatively low reservoir properties to the NW of the field. The reservoir heterogeneity is also measured using the Dykstra-Parsons technique which indicates extremely high heterogeneity (0.89 ≤ V ≤ 0.98).

4.
Vaccines (Basel) ; 11(11)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38005987

RESUMO

The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness.

5.
Mymensingh Med J ; 32(4): 1178-1183, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37777918

RESUMO

Covid-19 has become a pandemic since its emergence in Wuhan, China. It involves Gastro intestinal (GI) system and diarrhea is recognized as an important symptom. Diarrhea is also associated with disease severity. This study was conducted to see the prevalence of diarrhea in Covid-19 positive patient and its relation with disease severity. Prospective observational study done among consecutive Covid-19 positive patient of both sex admitted in Mugda Medical College Hospital in Dhaka from February 2021 to April 2021. Informations were collected by face to face interview and severity was assessed on bedside. Among 166 Covid-19 positive patient 40.0% developed diarrhea. Mean age of the diarrheal patients was 44.21±14.40. Women affected more than men (51.0% versus 49.0%). In majority patient (62.0%) diarrhea persist for 3-7 days and majority had frequency of bowel movement 3-5 times per day. Regarding Bristol stool type 47.0% had stool type 6 followed by stool type 7(43.0%) and stool type 5(10.0%). Half of the diarrheal patient (48.0%) had severe pneumonia. Severe pneumonia is significantly more common in non-diarrheal patients (65.0%) than in diarrheal patient (35.0%) (p=0.007). This study reflects that a large number of Covid-19 positive patients developed diarrhea. Half of the diarrheal patients had severe pneumonia. But severe pneumonia is significantly common in non-diarrheal patient than diarrheal patients.


Assuntos
COVID-19 , Masculino , Humanos , Feminino , Prevalência , COVID-19/complicações , COVID-19/epidemiologia , Bangladesh/epidemiologia , Diarreia/epidemiologia , Diarreia/etiologia , Hospitais
6.
Eur Rev Med Pharmacol Sci ; 26(7): 2313-2329, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35442486

RESUMO

OBJECTIVE: To investigate the impact of alpha-lipoic acid (ALA) on inflammation, oxidative stress, anemia, and glycemic parameters and their association with cardiovascular risk in diabetic patients on hemodialysis. PATIENTS AND METHODS: In this multi-center, randomized, controlled study, 60 diabetic patients on hemodialysis were randomized into control group (n=30) which received Epoetin-alpha plus insulin therapy, and alpha-lipoic acid group (n=30) which received the same treatment plus alpha-lipoic acid (ALA) 600 mg once daily. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), creatinine, urea, blood urea nitrogen (BUN), hemoglobin (Hb), iron parameters, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and fructosamine were measured at baseline and six months after intervention. The ankle-brachial index (ABI) was used to evaluate the clinical outcome. Erythropoietin resistance index (ERI), the weekly cost of Epoetin-alpha doses, and the total cost were calculated. RESULTS: The two groups were statistically similar at baseline. After the intervention, as compared to the control group, ALA group showed significant reductions in serum levels of hs-CRP, TNF-α, 8-OHdG (p<0.001), urea, and BUN (p=0.029) with significant elevations in Hb concentration (p<0.001), serum iron (p=0.037) and transferrin saturation (p<0.001). ALA group showed a significant decline in FBG (p=0.004), HbA1c (p<0.001), fructosamine (p=0.005), ERI (p<0.001), weekly doses, and the weekly cost of Epoetin-alpha, and the total cost (p<0.001). ALA provided a cardio-protective effect, whereas the percentage of patients with acceptable ABI (0.9-1) was significantly higher in ALA group than in the control group (p=0.024), and those with abnormally low ABI (<0.9) were lower in the ALA group. CONCLUSIONS: Due to its efficacy and safety, alpha-lipoic acid represents a pharmaco-economic supplement for diabetic patients on hemodialysis. Further trials are needed for complete evaluation of ALA effects.


Assuntos
Anemia , Doenças Cardiovasculares , Diabetes Mellitus , Eritropoetina , Ácido Tióctico , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Eritropoetina/uso terapêutico , Frutosamina , Hemoglobinas Glicadas , Controle Glicêmico , Fatores de Risco de Doenças Cardíacas , Humanos , Ferro/uso terapêutico , Estudos Prospectivos , Diálise Renal/efeitos adversos , Fatores de Risco , Ácido Tióctico/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Ureia
7.
Front Immunol ; 13: 838985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281011

RESUMO

Introduction: Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited. Materials and methods: To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2. Results: At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses. Conclusions: SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina BNT162/imunologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Monitorização Fisiológica/métodos , SARS-CoV-2/imunologia , Idoso , Anticorpos Antivirais/sangue , ELISPOT , Feminino , Humanos , Imunidade Celular , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo , Vacinação
8.
Mymensingh Med J ; 30(3): 744-750, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226464

RESUMO

Eosinophilic esophagitis (EoE) is a disease of modern era. It was first described 40 years back. Since then it has drawn an immense interest among the clinicians. It is diagnosed by the presence of eosinophils count ≥15/HPF on esophageal biopsied mucosa in patients with symptoms of esopohageal dysfunction. It is more prevalent among patients with gastroesophageal reflux disease. As its symptoms overlap with that of gastroesophageal reflux disease (GERD), it is frequently overlooked & misdiagnosed which increases patients' sufferings. No data is available in Bangladesh. The objective of the study was to find out the frequency of eosinophilic esophagitis among patients with gastroesophageal reflux symptoms. The study was conducted at the Outpatient department of the department of Gastroenterology of Dhaka Medical College Hospital, Dhaka, Bangladesh from September 2018 to April 2019. One hundred and thirty three (133) consecutive patients with symptoms suggestive of gastroesophageal reflux disease based on validated questionnaire underwent upper GI endoscopy. Biopsies were taken from proximal and distal esophagus as well as any other endoscopically abnormal esophageal mucosal lesion. Among 133 patients with gastroesophageal reflux symptoms, 7 patients (5.3%) were found to be positive for eosinophilic esophagitis. Mean age at diagnosis was 37.28±13.38 years. It was more common in younger age group. Female patients (56%) were more than male patients (44%). Heart burn was the major symptom followed by acid regurgitation. Nocturnal cough showed statistically significant relationship with eosinophilic esophagitis. Although the frequency is low, it may be considered as a differential diagnosis among patients with GERD.


Assuntos
Esofagite Eosinofílica , Refluxo Gastroesofágico , Bangladesh/epidemiologia , Estudos Transversais , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/epidemiologia , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Hospitais , Humanos , Masculino
9.
Am J Transplant ; 21(5): 1893-1901, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33421294

RESUMO

Following solid organ transplantation, a substantial proportion of chronic allograft loss is attributed to the formation of donor-specific antibodies (DSAs) and antibody-mediated rejection (AbMR). The frequency and phenotype of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells is altered in the setting of kidney transplantation, particularly in patients who develop AbMR. However, the roles of Tfh and Tfr cells in AbMR after solid organ transplantation is unclear. We developed mouse models to inducibly and potently perturb Tfh and Tfr cells to assess the roles of these cells in the development of DSA and AbMR. We found that Tfh cells are required for both de novo DSA responses as well as augmentation of DSA following presensitization. Using orthotopic allogeneic kidney transplantation models, we found that deletion of Tfh cells at the time of transplantation resulted in less severe transplant rejection. Furthermore, using inducible Tfr cell deletion strategies we found that Tfr cells inhibit de novo DSA formation but only have a minor role in controlling kidney transplant rejection. These studies demonstrate that Tfh cells promote, whereas Tfr cells inhibit, DSA to control rejection after kidney transplantation. Therefore, targeting these cells represent a new therapeutic strategy to prevent and treat AbMR.


Assuntos
Transplante de Rim , Transplante de Órgãos , Animais , Anticorpos , Rejeição de Enxerto/etiologia , Humanos , Transplante de Rim/efeitos adversos , Camundongos , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos
10.
Curr Opin Organ Transplant ; 25(1): 22-26, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789953

RESUMO

PURPOSE OF REVIEW: To summarize recent studies elucidating the roles of follicular T cells in controlling allospecific antibody responses and antibody-mediated rejection (AbMR). RECENT FINDINGS: The field of antibody regulation has provided an in depth identification of the T-cell subsets involved in regulation of antibody responses. In addition, tools have been developed to study these cells during disease. Over the past few years, these strategies have been implemented in the field of transplantation to study the roles of T cells in mediating pathogenic antibody responses. SUMMARY: AbMR is largely responsible for long-term graft failure after solid organ transplantation and is induced by allospecific antibodies. In vaccination and infection, antiboody responses are controlled by humoral immunoregulation in which T follicular helper (Tfh) cells promote, and T follicular regulatory (Tfr) cells inhibit, antibody responses. Recent studies have suggested multifaceted roles for follicular T-cell subsets in regulating allospecific antibody responses and AbMR during organ transplantation. In addition, we discuss research priorities for the field to help elucidate mechanisms used by these cells so that new targeted therapeutics can be developed to prevent AbMR in human organ transplantation.


Assuntos
Isoanticorpos/imunologia , Linfócitos T Reguladores/imunologia , Humanos
11.
Nat Immunol ; 20(10): 1360-1371, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31477921

RESUMO

Follicular regulatory T (TFR) cells have specialized roles in modulating follicular helper T (TFH) cell activation of B cells. However, the precise role of TFR cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A TFR cell-deleter mouse was developed that selectively deletes TFR cells, facilitating temporal studies. TFR cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of TFR cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of TFR cells in house dust mite models. TFR cells were found to control TFH13 cell-induced IgE. In vivo, loss of TFR cells increased house-dust-mite-specific IgE and lung inflammation. Thus, TFR cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.


Assuntos
Linfócitos B/imunologia , Centro Germinativo/imunologia , Hipersensibilidade/imunologia , Pneumonia/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Autoantígenos/imunologia , Deleção Clonal/genética , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Imunidade Humoral , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Memória Imunológica , Interleucina-13/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pyroglyphidae/imunologia
12.
J Sex Med ; 16(3): 383-393, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30846112

RESUMO

BACKGROUND: Previous studies have documented improvement in erectile function after bilateral cavernous nerve injury (BCNI) in rats with the use of pioglitazone. Our group determined this improvement to be mediated by the insulin-like growth factor-1 (IGF-1) pathway. AIM: To eliminate the systemic effects of pioglitazone and evaluate the local delivery of IGF-1 by polymeric microspheres after BCNI in the rat. METHODS: Male Sprague-Dawley rats aged 10-12 weeks were assigned at random to 3 groups: sham operation with phosphate buffered saline (PBS)-loaded microspheres (sham group), crush injury with PBS-loaded microspheres (crush group), and crush injury with IGF-1-loaded microspheres (IGF-1 group). Poly(lactic-co-glycolic) acid microspheres were injected underneath the major pelvic ganglion (MPG). IGF-1 was released at approximately 30 ng/mL/day per MPG per rat. OUTCOMES: Functional results were demonstrated by maximal intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP). Protein-level analysis data of IGF-1 receptor (IGF-1R), extracellular signal-regulated kinase (ERK)-1/2, and neuronal nitric oxide synthase (nNOS) were obtained using Western blot analysis and immunohistochemistry for both the cavernosal tissue and the MPG and cavernous nerve (CN). RESULTS: At 2 weeks after nerve injury, animals treated with IGF-1 demonstrated improved erectile functional recovery (ICP/MAP) at all voltages compared with BCNI (2.5V, P = .001; 5V, P < .001; 7.5V, P < .001). Western blot results revealed that up-regulation of the IGF-1R and ERK-1/2 in both the nervous and erectile tissue was associated with improved erectile function recovery. There were no significant between-group differences in nNOS protein levels in cavernosal tissue, but there was an up-regulation of nNOS in the MPG and CN. Immunohistochemistry confirmed these trends. CLINICAL TRANSLATION: Local up-regulation of the IGF-1R in the neurovascular bed at the time of nerve injury may help men preserve erectile function after pelvic surgery, such as radical prostatectomy, eliminating the need for systemic therapy. STRENGTHS & LIMITATIONS: This study demonstrates that local drug delivery to the MPG and CN can affect the CN tissue downstream, but did not investigate the potential effects of up-regulation of the growth factor receptors on prostate cancer tissue. CONCLUSION: Stimulating the IGF-1R at the level of the CN has the potential to mitigate erectile dysfunction in men after radical prostatectomy, but further research is needed to evaluate the safety of this growth factor in the setting of prostate cancer. Haney NM, Talwar S, Akula PK, et al. Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury. J Sex Med 2019;16:383-393.


Assuntos
Disfunção Erétil/tratamento farmacológico , Fator de Crescimento Insulin-Like I/administração & dosagem , Ereção Peniana/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Disfunção Erétil/fisiopatologia , Plexo Hipogástrico/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Microesferas , Óxido Nítrico Sintase Tipo I/metabolismo , Pênis/fisiopatologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos do Sistema Nervoso/tratamento farmacológico
13.
Eur J Pharm Biopharm ; 133: 42-62, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30300719

RESUMO

Complex nanosystems fabricated by hybridization of different types of materials such as lipids, proteins, or polysaccharides are usually superior to simple ones in terms of features and applications. Proteins and polysaccharides hold great potential for development of nanocarriers for drug delivery purposes based on their unique biocompatibility, biodegradability, ease of functionalization, improved biodistribution and minimal toxicity profiles. Protein-polysaccharide nanohybrids have gained a lot of attention in the past few years particularly for drug delivery applications. In this review, different hybridization techniques utilized in the fabrication of such nanohybrids including electrostatic complexation, Maillard conjugation, chemical coupling and electrospinning were thoroughly reviewed. Moreover, various formulation factors affecting the characteristics of the formed nanohybrids were discussed. We also reviewed in depth the outcomes of such hybridization ranging from stability enhancement, to toxicity reduction, improved biocompatibility, and drug release modulation. We also gave an insight on their limitations and what hinders their clinical translation and market introduction.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Polissacarídeos/química , Proteínas/química , Tecnologia Farmacêutica/métodos , Animais , Portadores de Fármacos/química , Humanos
14.
Trop Anim Health Prod ; 50(5): 1079-1087, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29423707

RESUMO

This experiment was conducted to study the effect of reproductive disorders on reproductive efficiency and milk production in relation with pro-inflammatory cytokines in dromedary she-camels. Total of 20 late pregnant Maghrabi she-camels, aging 6-9 years, weighing 420-550 kg, and between the second and third parities were divided into two groups. Animals in the first group (n = 12) showed normal reproductive status (G1) at parturition, while those in the second one (n = 8) were suffered from reproductive disorders after parturition (G2). Results showed that during pre-partum, red blood cells (RBCs) count decreased (P ≤ 0.05), while white blood cells (WBCs), packed cell volume (PCV) value, and neutrophils percentage increased (P ≤ 0.05) in G2 than in G1. Percentages of monocytes, basophils, and eosinophils as well as hemoglobin concentration did not differ significantly (P ≥ 0.05) in G1 and G2. During postpartum period, the same results were noticed in addition to increase (P ≤ 0.05) in eosinophil and decrease (P ≤ 0.05) in basophils percentages. During prepartum period, concentration of total proteins, albumin (AL) and IGF-1decreased (P ≤ 0.05), cholesterol concentration, and activity of AST and ALT were higher (P ≤ 0.05) in G2 than in G1. Globulin (GL), AL: GL ratio, glucose, urea-N, creatinine, and triglyceride concentrations did not differ significantly in G1 and G2. During postpartum period, the same results were noticed with decrease (P ≤ 0.05) in GL and glucose concentrations in G2 as compared to G1. Concentration of all pro-inflammatory cytokines, including IL-6, IL-10, and IFN-γ, was higher (P ≤ 0.05) in G2 than in G1 at different peri-parturient times. Milk yield, days in milk, protein and lactose percentages, and IgG concentration were higher (P ≤ 0.05) in G1 than in G2. Fat, total solids, solid non-fat, and ash percentages did not show any significant differences between both groups. Reproductive traits, including length of estrous cycle, duration of estrous period, number of services/conception, gestation period, days open, and conception rate, were higher (P < 0.05) in G1 than in G2. From the present study can be concluded that pro-inflammatory cytokines may be a necessary test for the early diagnosis to prevent related disease in dromedary camels suffering from reproductive disorders. This study indicated strong relationship between hematological parameters and concentration of blood biochemicals and cytokines with reproductive efficiency in camels, which may be helpful in elucidating the adverse effects associated with reproductive disorders.


Assuntos
Camelus/fisiologia , Citocinas/sangue , Infertilidade Feminina/sangue , Leite/química , Reprodução/efeitos dos fármacos , Animais , Camelus/sangue , Colesterol/sangue , Eritrócitos/citologia , Estro , Feminino , Fertilização , Lactose , Parto , Período Pós-Parto , Gravidez , Prenhez , Triglicerídeos
15.
Andrology ; 6(2): 301-305, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29359516

RESUMO

In a case-controlled study, we assessed the expressed seminal NAD-dependent protein deacetylase (SIRT1) expression in infertile oligoasthenoteratozoospermic (OAT) men associated with varicocoele. Our study involved 81 men, recruited from the University hospitals, after ethical approval and informed consent. They were allocated into fertile normozoospermic men (n = 23), infertile OAT men without varicocoele (n = 23) and infertile OAT men with varicocoele (n = 35). Inclusion criteria consisted of confirmation of abnormal semen parameters and normal female partners whereas exclusion criteria were leukocytospermia, tobacco smoking, hormonal therapy, immunological disorders, dyslipidemia, hypogonadism, cardiovascular disorders, morbid obesity, and hepatic or renal failures. All participants had an interview to assess clinical history, clinical examination, semen analysis, and estimation of seminal SIRT1 expression. Seminal SIRT1 expression was significantly lower in infertile OAT men than fertile men. Among infertile OAT men, seminal SIRT1 expression was significantly lower in those with varicocoele than in those without. Additionally, seminal SIRT1 expression was significantly lower in varicocoele grade III cases compared with other grades. Seminal SIRT1 expression was positively correlated with sperm concentration (r = 0.327, p = 0.001), total sperm motility (r = 0.532, p = 0.001), and sperm normal forms (r = 0.469, p = 0.001). Our results suggest that seminal SIRT1 expression has a role of male infertility being significantly decreased in infertile OAT men in general and in infertile OAT men associated with varicocoele in particular.


Assuntos
Infertilidade Masculina/metabolismo , Sêmen/metabolismo , Sirtuína 1/biossíntese , Varicocele/metabolismo , Adulto , Astenozoospermia/metabolismo , Azoospermia/metabolismo , Estudos de Casos e Controles , Humanos , Infertilidade Masculina/complicações , Masculino , Oligospermia/metabolismo , Varicocele/complicações
16.
Andrology ; 6(1): 146-150, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29195028

RESUMO

This study aimed to assess the effect of varicocelectomy and/or mast cells (MCs) stabilizer on sperm DNA fragmentation in infertile men with varicocele (Vx). Overall, 120 infertile patients were randomized to three equal treatment arms; patients that underwent varicocelectomy, patients on 1 mg ketotifen twice daily for three months, and patients that underwent varicocelectomy followed with 1 mg ketotifen twice daily for three months. These patients were subjected to history taking, clinical examination, semen analysis, and estimation of sperm DNA fragmentation index (DFI). After 3 months, all investigated groups showed significant improvement regarding the mean total sperm count, sperm concentration, total sperm motility, and sperm normal forms percentage compared with the pre-treatment data. As well, the mean sperm DFI was significantly improved compared with the pre-treatment data; in men that underwent varicocelectomy (34.6% vs. 28.3%), in men on MC stabilizer only (33.4% vs. 27.8%), and in men that underwent varicocelectomy followed by MC stabilizer (34.3% vs. 25.1%). Sperm DFI improvement percentages showed the highest improvement in men that underwent varicocelectomy followed with MC stabilizer compared with the other two groups (26.8% vs. 18.2%, 16.8%). Sperm DFI improvement percentages showed significant increases in the infertile patients with Vx grade III compared to Vx grade II in all investigated groups. It is concluded that in infertile men associated with Vx and high sperm DFI, surgical repair followed with MCs stabilizer significantly improve sperm DFI compared with either surgical repair or MCs stabilizer alone.


Assuntos
Fragmentação do DNA/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Infertilidade Masculina/terapia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Varicocele/terapia , Adulto , Terapia Combinada/métodos , Humanos , Infertilidade Masculina/etiologia , Cetotifeno/uso terapêutico , Masculino , Mastócitos/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Varicocele/complicações
17.
Andrologia ; 50(2)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28786126

RESUMO

Puberty is the transitional period between childhood and adulthood, a process encompassing morphological, physiological and behavioural development to attain full reproductive capability. This study aimed to assess serum relaxin-3 hormone relationship with male delayed puberty. Sixty males were investigated as two equal groups: males with delayed puberty and healthy matched males as controls. They were subjected to history taking, clinical examination and estimation of serum FSH, LH, testosterone, relaxin-3 hormonal levels. The results showed that the secondary sexual characters in the patients group were at Tanner stages 1-2 and in the healthy controls at Tanner stages 3-5. The mean BMI in the patients group was significantly increased, whereas the mean levels of the span, testicular volume, serum LH, FSH, testosterone as well as relaxin-3 hormonal levels were significantly decreased compared with the healthy controls. Serum relaxin-3 levels showed significant positive correlation with the age, testis volume, span, Tanner stages, serum testosterone, FSH, LH hormones. In addition, serum relaxin-3 levels showed significant negative correlation with BMI. It is concluded that serum level of relaxin-3 hormone is an important mediator in the pathophysiological process of normal puberty being significantly decreased in males with delayed puberty.


Assuntos
Puberdade Tardia/sangue , Puberdade/fisiologia , Relaxina/sangue , Adolescente , Fatores Etários , Índice de Massa Corporal , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Puberdade Tardia/fisiopatologia , Relaxina/fisiologia , Testosterona/sangue
18.
Andrologia ; 49(3)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27246870

RESUMO

This study aimed to assess seminal mast cells in infertile men associated with varicocele (Vx) pre- and post-surgical repair. Forty-five infertile men associated with Vx were subjected to history taking and clinical examination. In addition, semen parameters and seminal mast cells stained with 1% toluidine blue were estimated pre-varicocelectomy and three months post-varicocelectomy. Vx surgical repair revealed a significant improvement in the mean sperm concentration, progressive sperm motility, total sperm motility and sperm abnormal morphology and a significant decrement in seminal mast cells (mean ± SD, 3.56 ± 2.23 cells per high-power field (HPF) vs. 2.22 ± 1.06 cells per HPF, p = .01). The pre-operative mean mast cell count demonstrated significant increases in cases with Vx grade III compared with other Vx grades and in cases with bilateral Vx compared with unilateral Vx cases. Seminal mast cells demonstrated a significant correlation with sperm concentration, progressive sperm motility and total sperm motility and a nonsignificant correlation with age and sperm abnormal morphology. It is concluded that seminal mast cells decrease significantly in infertile men with Vx after surgical repair showing a significant negative correlation with sperm concentration, progressive sperm motility and total sperm motility.


Assuntos
Mastócitos/citologia , Sêmen/citologia , Varicocele/cirurgia , Adulto , Contagem de Células , Feminino , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/imunologia , Masculino , Gravidez , Análise do Sêmen , Resultado do Tratamento , Varicocele/complicações , Procedimentos Cirúrgicos Vasculares , Adulto Jovem
19.
Andrologia ; 48(3): 355-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26228802

RESUMO

This study aimed to identify seminal Corynebacterium strains in infertile men with and without leucocytospermia. Semen samples from 60 infertile men were allocated into two equal groups: semen samples with leucocytospermia and semen samples without leucocytospermia. Semen culture for Corynebacterium species was carried out on Columbia agar medium confirmed by Gram-stained film and biochemical tests followed by analytical profile index biotyping and antibiotic susceptibility. Bacterial isolates were detected in 20/60 semen cultures (33.3%) as Corynebacteria, Staphylococci, Alpha haemolytic streptococci and E. coli. In all, 12/60 (20%) had Corynebacterium positive semen culture, whereas C. seminal was the major isolated species followed by C. amycolatum, C. jekium and C. urealyticum. There was nonsignificant difference between patients with/without Corynebacterium positive culture regarding sperm concentration and normal sperm morphology; however, in positive cultures sperm motility was significantly lower compared with negative cultures. Antimicrobial sensitivity among Corynebacteria strains was highest for vancomycin, rifampicin then imipenem, ampicillin + sulbactam, ciprofloxacin. It is concluded that positive semen cultures for different Corynebacteria species were demonstrated in infertile men, whereas Corynebacterium seminale was the most common isolated species. Vancomycin, rifampicin then imipenem and ampicillin + sulbactam are recommended as sensitive antibiotics.


Assuntos
Corynebacterium/isolamento & purificação , Infertilidade Masculina/microbiologia , Sêmen/microbiologia , Adulto , Estudos Transversais , Humanos , Infertilidade Masculina/etiologia , Masculino , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Adulto Jovem
20.
Andrologia ; 48(2): 137-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25906828

RESUMO

This study aimed to assess the relation of seminal cyclooxygenase COX-1, COX-2 with oxidative stress in infertile oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). In all, 128 men were allocated into fertile men, fertile men with Vx, infertile OAT men without Vx and infertile OAT men with Vx. They were subjected to history taking, clinical examination and semen analysis. Also, seminal COX-1, COX-2, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated. Mean levels of seminal COX-1, COX-2 were over-expressed, the mean level of seminal MDA was significantly increased, and the mean level of seminal GPx was significantly decreased in infertile OAT men with Vx compared with other groups. Seminal COX-1 and COX-2 were over-expressed in cases with Vx grade III compared with Vx grades I, II cases and in cases with bilateral Vx compared with unilateral Vx. There was significant negative correlation between seminal COX-1 and COX-2 with sperm concentration, sperm motility, sperm normal morphology, seminal GPx and significant positive correlation with seminal MDA. It is concluded that seminal COX-1 and COX-2 are over-expressed in infertile OAT men with Vx compared with fertile men with/without and infertile OAT men without Vx being associated with oxidative stress, Vx grade and Vx laterality.


Assuntos
Astenozoospermia/enzimologia , Infertilidade Masculina/enzimologia , Oligospermia/enzimologia , Estresse Oxidativo , Sêmen/enzimologia , Varicocele/enzimologia , Adulto , Astenozoospermia/complicações , Astenozoospermia/metabolismo , Estudos de Casos e Controles , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Infertilidade Masculina/complicações , Infertilidade Masculina/metabolismo , Masculino , Malondialdeído/metabolismo , Oligospermia/complicações , Oligospermia/metabolismo , Varicocele/complicações , Varicocele/metabolismo , Adulto Jovem
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