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1.
Drug Dev Res ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785110

RESUMO

The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and ß and three distinct subtypes of ß receptor: ß1-, ß2-, and ß3-adrenoceptors. The ß adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi ßγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.

2.
J Environ Pathol Toxicol Oncol ; 38(2): 133-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679276

RESUMO

The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias Colorretais/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/efeitos adversos , Transdução de Sinais/efeitos dos fármacos
3.
J Environ Pathol Toxicol Oncol ; 38(2): 143-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679277

RESUMO

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.


Assuntos
Cardiotônicos/farmacologia , Cardiotoxinas/toxicidade , Doxorrubicina/toxicidade , Genisteína/farmacologia , Heme Oxigenase-1/genética , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Cardiotoxicidade/etiologia , Heme Oxigenase-1/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Wistar
4.
Biotechnol Appl Biochem ; 66(5): 715-719, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31314127

RESUMO

Homocysteine [HSCH2 CH2 CH(NH2 )COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Creatinina/sangue , Ácido Fólico/farmacologia , Hiper-Homocisteinemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Ácido Úrico/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hipertensão/sangue , Estudos Observacionais como Assunto
5.
Chem Biol Interact ; 306: 117-122, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31004596

RESUMO

Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.


Assuntos
Demência/complicações , Demência/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Animais , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/agonistas , Ilhotas Pancreáticas/metabolismo
6.
Anat Sci Int ; 83(4): 277-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19159358

RESUMO

Presented herein is a case of an extremely rare muscle in the pectoral region. It involved an accessory muscular slip originating from the pectoralis major and inserting onto the medial epicondyle of the humerus and the medial intermuscular septum. According to the literature this muscle is defined as chondroepitrochlearis. The arterial and nervous supply to the muscle came from the lateral thoracic artery and the medial pectoral nerve, respectively. Clinical considerations of such a variation include ulnar nerve entrapment and functionally limited abduction of the humerus.


Assuntos
Músculos Peitorais/anormalidades , Humanos , Úmero/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Músculos Peitorais/irrigação sanguínea , Músculos Peitorais/inervação , Artérias Torácicas/anatomia & histologia , Nervos Torácicos/anatomia & histologia
7.
Mutat Res ; 607(2): 240-52, 2006 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-16793327

RESUMO

Treatment of cancers with cytotoxic agents such as alkylating drugs often, but not always results in transient to permanent testicular dysfunction. The present study was planned to investigate the effects of dacarbazine [5-(3,3-dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100mg/kg body weight/day dacarbazine (i.p.) for 5 days at intervals of 24h between treatments. Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm motility, sperm morphology, testicular histopathology (qualitative histopathology, seminiferous tubular diameter and epithelial height), and intra-testicular levels of testosterone and lactate dehydrogenase were assessed. Dacarbazine decreased the body weight only on day 28 at 25mg/kg dose-level, but increased the paired testes weights at 50mg/kg on day 7, at 25-100mg/kg on day 14, and at 25 and 50mg/kg on day 21 (P<0.05-0.01; one-way ANOVA and Bonferroni's post hoc test). The sperm count was decreased on all sampling days except at 5 and 25mg/kg dose-levels on day 70, but with severe oligospermia on days 28 and 35 (P<0.05-0.001). The sperm motility was decreased at 100mg/kg on days 14 and 21, at 5, 25, and 100mg/kg on day 28, and at all dose-levels on day 35 (P<0.05-0.001). Dacarbazine induced both head and tail abnormalities and some sperms with cytoplasmic droplets, but significant increase was seen in all dose groups on days 14 and 21, and at 100mg/kg dose-level on day 35. Drug-induced epithelial sloughing was seen on days 14-35 and other histopathological changes observed were vacuoles and abnormal cells. The STD was increased at 25-100mg/kg on day 7, at all dose-levels on day 14, at 50-100mg/kg on days 21 and 28, but without any effects on days 35-70 (P<0.05-0.001), and the tubular lumen was found dilated. The SE was increased on days 7, 21 and 28 at 100mg/kg and on day 14 at 50-100mg/kg. Dacarbazine reduced the intra-testicular testosterone level at 100mg/kg on day 7, at 5, 50 and 100mg/kg on day 14, at all dose-levels on days 21, 28, and 35, and at 50mg/kg on day 49 (P<0.05-0.001). The intra-testicular lactate dehydrogenase concentration increased at all dose-levels up to day 35, but without any effect on days 49 and 70 (P<0.05-0.001). There was no particular dose-response of dacarbazine on any parameters tested. The sperm count (except on day 7-positive correlation; Pearson product moment correlation) or sperm motility did not have any relation but increase in abnormal sperms showed negative correlation with decrease in testosterone level on days 7, 21 and 28. Decrease in sperm count was in negative correlation on days 14 and 35, and increase in abnormal sperms showed positive correlation on day 35 with increase in LDH level. Finally, the decrease in sperm motility had no correlation with increase in abnormal sperm shapes. We conclude that dacarbazine is genotoxic and cytotoxic to the mouse testis in a transient fashion, and these effects are exerted along with decrease in testosterone and increase in lactate dehydrogenase levels in the testis.


Assuntos
Dacarbazina/toxicidade , L-Lactato Desidrogenase/metabolismo , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testosterona/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epididimo/citologia , Epididimo/efeitos dos fármacos , Masculino , Camundongos , Oligospermia/induzido quimicamente , Tamanho do Órgão/efeitos dos fármacos , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia
8.
Clin Anat ; 19(6): 566-8, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16283657

RESUMO

Variations in the origin of arteries in the abdomen are very common. The arteries that show frequent variations include the celiac trunk, renal arteries, and gonadal arteries. We observed multiple variations in a 45-year-old male cadaver. The variations found on the left side were: one accessory renal artery, two testicular arteries, and middle suprarenal and inferior phrenic arteries that branched from the celiac trunk. On the right side, the inferior phrenic and middle suprarenal arteries arose from the right renal artery.


Assuntos
Aorta Abdominal/anatomia & histologia , Artéria Renal/anormalidades , Aorta Abdominal/patologia , Cadáver , Humanos , Masculino , Pessoa de Meia-Idade
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