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Journal of Postgraduate Medicine Apr 2024Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM...
CONTEXT/AIMS
Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM parameters is limited. We aimed to describe ABPM parameters in a cohort of PPGL at our center in western India.
METHODS
Retrospective study of patients with PPGL whose ABPM data was available. Demographic details, secretory status, and ABPM data were retrieved. Coefficient of variability (CV) was calculated as standard deviation/mean in percentage.
RESULTS
In the 39 included patients, mean age at presentation was 39.3 ± 14.2 yr; 20 (51.3%) were males, 25 (64.1%) hypertensive, and mean tumor diameter was 5.3 cm. In 18 patients whose baseline ABPM was done without medications, those with nocturnal blood pressure dipping (6/18, 33%) had higher serum metanephrines (median 313.2 vs. 34.7 pg/ml, P = 0.028). Despite normal office blood pressure (BP), 8.9% of systolic BP readings were >140 mmHg, and 1.2% were >160 mmHg. Among 29 patients with both pre and post-block ABPM, mean BP (systolic 121.6 vs. 132.5 mmHg, P = 0.014; diastolic 68.9 vs. 76.4 mmHg, P = 0.005) and percentage of BP readings above 140 mmHg (median 9.4% vs. 24.4%, P = 0.016) were significantly lowered after the preoperative blockade in hypertensive ( n = 19) patients, whereas CV was similar. The post-blockade ABPM characteristics were similar in patients blocked with amlodipine or prazosin.
CONCLUSION
ABPM provides additional information about BP characteristics in PPGL. The preoperative blocking decreases the magnitude of BP excursions but does not affect BP variability.
Topics: Humans; Pheochromocytoma; Male; Female; Blood Pressure Monitoring, Ambulatory; Adult; Retrospective Studies; Middle Aged; Adrenal Gland Neoplasms; Paraganglioma; Hypertension; Blood Pressure; India
PubMed: 37555422
DOI: 10.4103/jpgm.jpgm_208_23 -
JFMS Open Reports 2024An 8-month-old female spayed domestic shorthair cat was presented for chronic urinary incontinence (UI). Since being adopted 6 months earlier, the cat had a history of...
CASE SUMMARY
An 8-month-old female spayed domestic shorthair cat was presented for chronic urinary incontinence (UI). Since being adopted 6 months earlier, the cat had a history of urine leakage during both activity and rest. Baseline blood work and urine culture showed no significant abnormalities and no evidence of a urinary tract infection. An abdominal CT with excretory urography followed by a focal urinary tract ultrasound revealed a suspected right intramural ectopic ureter (EU) and potential left EU. Cystoscopy confirmed bilateral intramural EUs. Cystoscopic-guided laser ablation (CLA) of both EUs was performed. The cat developed temporary urinary obstruction (UO) 36 h after the procedure, which was medically managed with prazosin and buprenorphine. Ultimately, the cat's urinary signs completely resolved with no UI recognized after the procedure and the cat has remained continent during 18 months of follow-up.
RELEVANCE AND NOVEL INFORMATION
CLA of intramural EUs is routinely performed in dogs, but this technique has not been previously reported in cats with this condition. Although post-procedural urinary tract signs were initially present, the cat ultimately had an excellent outcome with resolution of UI after this procedure.
PubMed: 38322250
DOI: 10.1177/20551169231220248 -
Pharmaceuticals (Basel, Switzerland) May 2024Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant...
Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α-adrenergic receptors, and 5-HT receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.
PubMed: 38794158
DOI: 10.3390/ph17050588 -
Anti-cancer Drugs Nov 2023Anticancer drug resistance is one of the biggest hurdles in the treatment of breast cancer. Drug repurposing is a viable option fordeveloping novel medical treatment...
Anticancer drug resistance is one of the biggest hurdles in the treatment of breast cancer. Drug repurposing is a viable option fordeveloping novel medical treatment strategies since this method is more cost-efficient and rapid. Antihypertensive medicines have recently been found to have pharmacological features that could be used to treat cancer, making them effective candidates for therapeutic repurposing. The goal of our research is to find a potent antihypertensive drug that can be repurposed as adjuvant therapy for breast cancer. In this study, virtual screening was performed using a set of Food and Drug Administration (FDA)-approved antihypertensive drugs as ligands with selected receptor proteins (EGFR, KRAS, P53, AGTR1, AGTR2, and ACE) assuming these proteins are regarded to have a significant role in hypertension as well as breast cancer. Further, our in-silico results were further confirmed by an in-vitro experiment (cytotoxicity assay). All the compounds (enalapril, atenolol, acebutolol, propranolol, amlodipine, verapamil, doxazosin, prazosin, hydralazine, irbesartan, telmisartan, candesartan, and aliskiren) showed remarkable affinity towards the target receptor proteins. However, maximum affinity was displayed by telmisartan. Cell-based cytotoxicity study of telmisartan in MCF7 (breast cancer cell line) confirmed the anticancer effect of telmisartan. IC50 of the drug was calculated to be 7.75 µM and at this concentration, remarkable morphological alterations were observed in the MCF7 cells confirming its cytotoxicity in breast cancer cells. Based on both in-silico and in-vitro studies, we can conclude that telmisartan appears to be a promising drug repurposing candidate for the therapeutic treatment of breast cancer.
Topics: Humans; Female; Telmisartan; Pharmaceutical Preparations; Breast Neoplasms; Drug Repositioning; Antihypertensive Agents; Hypertension; Benzoates
PubMed: 36847075
DOI: 10.1097/CAD.0000000000001509 -
Nutrients Dec 2023Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Elevated serum concentrations of DCA are observed in cardiovascular disease (CVD). We...
BACKGROUND
Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Elevated serum concentrations of DCA are observed in cardiovascular disease (CVD). We hypothesized that DCA might influence hemodynamic parameters in rats.
METHODS
The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo.
RESULTS
The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/L. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds-prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor)-significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly.
CONCLUSIONS
DCA elevates BP primarily by augmenting cardiac output. As a metabolite derived from gut bacteria, DCA potentially serves as a mediator in the interaction between the gut microbiota and the host's circulatory system.
Topics: Male; Rats; Animals; Blood Pressure; Rats, Sprague-Dawley; Cardiac Output; Bile Acids and Salts; Deoxycholic Acid
PubMed: 38201862
DOI: 10.3390/nu16010032 -
Anticancer Research Aug 2023High grade gliomas are the most common and most lethal primary cancers of the central nervous system.
BACKGROUND
High grade gliomas are the most common and most lethal primary cancers of the central nervous system.
CASE REPORT
We herein present a case report of a long-term surviving 36-year-old female diagnosed with high grade glioma, for which she underwent neurosurgery with a gross total removal of the tumor. Shortly thereafter (<3 months) she was readmitted in a desolate state due to a large recurrence. After Ethical Committee approval, proper explanation, and consent from spouse, she was subjected to a reoperation involving a post-operative infusion into the excised tumor cavity, containing a mixture of a non-physiological amino acid in millimolar concentration and a proapoptotic drug in micromolar concentration. The patient tolerated the treatment well and was discharged in a stable state thereafter. A series of follow ups revealed successive clinical improvements and after 4-6 months, she had recovered with mild left hemiparesis, meaning that she was able to carry out activities of daily living independently. Now, 5.5 years later, after the recurrence and the infusion therapy, she continues to have a mild left hemiparesis and her MRI with contrast shows no evidence of tumor.
CONCLUSION
Continuous intratumoral infusion therapy with an artificial amino acid combined with a proapoptotic drug results in complete glioma cell lysis both in vitro and in vivo.
Topics: Humans; Female; Adult; Brain Neoplasms; Activities of Daily Living; Therapeutic Irrigation; Glioma; Paresis
PubMed: 37500132
DOI: 10.21873/anticanres.16537 -
Neuroscience Letters Feb 2024Terazosin is an α1-adrenergic receptor antagonist that can relax smooth muscle and is prescribed to treat benign prostatic hyperplasia and, rarely, hypertension. The...
Terazosin is an α1-adrenergic receptor antagonist that can relax smooth muscle and is prescribed to treat benign prostatic hyperplasia and, rarely, hypertension. The present study investigated the antidepressant-like actions of terazosin (TZ) in mice. They were first subjected to chronic unpredictable mild stress (CUMS) and then the effects of TZ were assessed using the forced swimming test (FST) and tail suspension test (TST), sucrose preference test (SPT), actophotometer test (APT). The changes in the PGK1 levels, neurotransmitters, and proinflammatory cytokines levels after chronic stress and TZ treatment were examined. It was found that TZ exhibited an antidepressant-like effect in the FST, TST, SPT, and APT. It was effective in the CUMS model of depression. It was also found that TZ treatment reduced the levels of proinflammatory cytokines and elevated the neurotransmitter levels in mice. Results of this study suggest that TZ has antidepressant-like actions in mice models of CUMS induced depression.
Topics: Mice; Animals; Depression; Antidepressive Agents; Prazosin; Cytokines; Stress, Psychological; Hippocampus; Disease Models, Animal; Behavior, Animal
PubMed: 38266974
DOI: 10.1016/j.neulet.2024.137653 -
Scientific Reports Jun 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
Topics: Animals; Female; Binge Drinking; Male; Rats; Disease Models, Animal; Rats, Wistar; Ethanol; Adrenergic Antagonists; Naltrexone; Propranolol; Sex Factors; Alcohol Drinking
PubMed: 38890353
DOI: 10.1038/s41598-024-64565-9 -
Advanced Biology Jun 2024Liver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective...
Liver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective therapeutics are lacking. Therefore, the study examines the effect of doxazosin on liver fibrosis. Carbon tetrachloride (CCl) is injected into mice to establish a liver fibrosis model. Doxazosin (5 and 10 mg/kg) is administered daily by gavage. HE staining, Masson staining, Sirius Red staining, scanning electron microscopy, western blotting, real-time PCR, and immunofluorescence analysis are performed to estimate liver fibrosis and sinusoidal capillarization in mice. Cell Counting Kit-8 assays, western blotting, immunofluorescence analysis, tube formation, and transwell migration assays are performed on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) to elucidate the potential mechanism of doxazosin. Doxazosin alleviates liver fibrosis and sinusoidal capillarization in CCl-induced mice. Angiogenesis is attenuated by doxazosin in HUVECs and HHSECs. This study demonstrates that doxazosin attenuated liver fibrosis by alleviating sinusoidal capillarization and liver angiogenesis.
Topics: Doxazosin; Animals; Mice; Liver Cirrhosis; Humans; Adrenergic alpha-1 Receptor Antagonists; Human Umbilical Vein Endothelial Cells; Male; Liver; Neovascularization, Pathologic; Carbon Tetrachloride; Mice, Inbred C57BL; Capillaries; Disease Models, Animal; Angiogenesis
PubMed: 38494421
DOI: 10.1002/adbi.202300513 -
Applied Biochemistry and Biotechnology Nov 2023Oral squamous cell carcinoma (OSCC), a global threatening disease, is reported mostly in the middle and elderly male population. Even though the exact cause of OSCC was...
Oral squamous cell carcinoma (OSCC), a global threatening disease, is reported mostly in the middle and elderly male population. Even though the exact cause of OSCC was not known, consumption of tobacco in any form has been reported in most of OSCC patients. OSCC is a massive invasive type of cancer which easily spreads to the distant organs. Hence treating it at appropriate time is necessary and the rate of OSCC incidence is also constantly increasing. At present, chemoradiation is the only therapy prescribed for OSCC patients which renders various side effects. Hence, the treatment with lesser side effect was of current research interest. Doxazosin (α1 adrenorecptor antagonist) had been proven to render anticancer effect in prostate, renal, hepatic, and ovarian cancers but its role in oral cancer cells was not been elucidated. Therefore, we have assessed the anticancer effect of doxazosin on oral squamous cancer cells via through the induction of apoptosis, and antioxidant property. The cytoprotective effect of doxazosin on normal Vero cells and anticancer effect on oral cancer KB cells were analyzed with MTT assay. Doxazosin antioxidant activity were analyzed by their reactivity with free radicals and metal ions by the method of FRAP, DPPH, chemilumiscence, and ORAC assay. The antioxidant levels were also assessed by TBARS, SOD, and glutathione levels, and later on apoptosis staining techniques like DCFH-DA, Rhodamine 123, and AO/EtBr stain were conducted. Apoptosis was confirmed by estimating the levels of apoptotic proteins in doxazosin-treated KB human oral cancer cells by ELISA method. The results from our study show that doxazosin is a potent antioxidant and it significantly induces apoptosis in human oral cancer by altering various cellular molecules at downstream signaling which has been depict in the results. Our study proves doxazosin as a potent anticancer drug which may be used in the treatment of oral carcinoma, if it is subjected to further research using human clinical trials.
Topics: Animals; Chlorocebus aethiops; Humans; Male; Aged; Doxazosin; Antioxidants; Adrenergic alpha-Antagonists; Carcinoma, Squamous Cell; Vero Cells; Prostatic Neoplasms; Mouth Neoplasms; Apoptosis; Cell Proliferation; Cell Line, Tumor
PubMed: 36943603
DOI: 10.1007/s12010-023-04412-1