- Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome. [Journal Article]
- JEJ Endocrinol Invest 2018 Nov 10
- CONCLUSIONS: The phenotypic variability of GS and therapeutic strategies deserve further research to improve GS diagnosis and prognosis. Even heterozygous carriers exhibited increased 24-h Na+ urine excretion, which may make them more susceptible to diuretic-induced hypokalemia.
- A Case of Recurrent Thrombotic Microangiopathy Caused by Hypertensive Urgency. [Journal Article]
- CCureus 2018 Aug 30; 10(8):e3235
- A 26-year-old man presented to the emergency room with abdominal pain, nausea, and vomiting for four days. His medical history was significant for hypertension and end-stage renal disease managed wit...
A 26-year-old man presented to the emergency room with abdominal pain, nausea, and vomiting for four days. His medical history was significant for hypertension and end-stage renal disease managed with hemodialysis. He had been noncompliant with the antihypertensive regimen which included nifedipine, hydralazine, and spironolactone. At presentation, his blood pressure was 231/123 mmHg. Laboratory workup showed white blood count 17.3 × 109/L (normal range: 4.5 to 11.0 × 109/L), hemoglobin 7.8 gm/dL (normal range: 13.5 to 17.5 g/dL), platelet count 46 × 109/L (normal range: 150 to 400 × 109/L), reticulocyte count 7.8%, total bilirubin 1 mg/dL (normal range: 0.1 to 1.2 mg/dL), lactate dehydrogenase 1,235 U/L (normal range: 140 to 280 U/L), haptoglobin < 10 mg/dL, and a direct Coomb's test was negative. Numerous schistocytes were identified on the peripheral blood smear. The patient was diagnosed with thrombotic microangiopathy secondary to severe hypertension and was started on intravenous nicardipine. With appropriate blood pressure control, hematological parameters improved with normalization of the platelet count within 10 days. Notably, the patient had one similar episode of hypertension-induced thrombotic microangiopathy within a period of the last three months and ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13) activity was normal on his previous admission.
- The prognosis of heart failure patients: Does sodium level play a significant role? [Journal Article]
- PlosPLoS One 2018; 13(11):e0207242
- CONCLUSIONS: In conclusion, hyponatremia is one of the crucial factors in the clinical prognosis of heart failure patients. However, as other prognostic factors (i.e. medication, creatine level, and age) also played vital roles in overall survival, well-controlled clinical trials (complete with medication dosing, laboratory outputs and long-term prospective follow up) are required to further study the impact of hyponatremia in HF patient's prognosis in low income nations.
- Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats. [Journal Article]
- JDJ Diabetes Res 2018; 2018:9232065
- Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mi...
Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-β1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.
- Screening and evaluation of antiviral compounds against Equid alpha-herpesviruses using an impedance-based cellular assay. [Journal Article]
- VVirology 2018 Oct 26; 526:105-116
- Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and ...
Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and sporadic abortion, while EHV-3 is responsible of equine coital exanthema. In view of the lack of efficacy of vaccines against EHV-1 and EHV-4 and in the absence of vaccines against EHV-3, the use of antiviral treatment is of great interest. In this study, we documented the interest of the Real-Time Cell Analysis (RTCA) technology to monitor the cytopathic effects induced by these viruses on equine dermal cells, and established the efficacy of this method to evaluate the antiviral effect of aciclovir (ACV) and ganciclovir (GCV). In addition, the RTCA technology has also been found appropriate for the high-throughput screening of small molecules against EHV, allowing the identification of spironolactone as a novel antiviral against EHV.
- Compatibility of Baclofen, Carvedilol, Hydrochlorothiazide, Mercaptopurine, Methadone Hydrochloride, Oseltamivir Phosphate, Phenobarbital, Propranolol Hydrochloride, Pyrazinamide, Sotalol Hydrochloride, Spironolactone, Tacrolimus Monohydrate, Ursodeoxycholic Acid, and Vancomycin Hydrochloride Oral Suspensions Compounded with SyrSpend SF pH4. [Journal Article]
- IJInt J Pharm Compd 2018 Nov-Dec; 22(6):516-526
- Compounded liquid medication is frequently required in children to allow easy dose adjustment and overcome swallowing difficulties. The objective of this study was to evaluate the stability of oral s...
Compounded liquid medication is frequently required in children to allow easy dose adjustment and overcome swallowing difficulties. The objective of this study was to evaluate the stability of oral suspensions compounded with SyrSpend SF PH4 and the commonly used active pharmaceutical ingredients baclofen 2.0 mg/mL, carvedilol 5.0 mg/mL, hydrochlorothiazide 2.0 mg/mL, mercaptopurine 10.0 mg/mL, methadone hydrochloride 10.0 mg/mL, oseltamivir phosphate 6.0 mg/mL, phenobarbital 9.0 mg/mL and 15.0 mg/mL, propranolol hydrochloride 0.5 mg/mL and 5.0 mg/mL, pyrazinamide 100.0 mg/mL, spironolactone 2.0 mg/mL and 2.5 mg/mL, sotalol hydrochloride 5.0 mg/mL, tacrolimus monohydrate 0.5 mg/mL, ursodeoxycholic acid 20.0 mg/mL, and vancomycin hydrochloride 25.0 mg/mL. Suspensions were compounded with raw powders, except for mercaptopurine, pyrazinamide, and sotalol hydrochloride, which were made from commercial tablets. Stability was assessed by measuring the percentage recovery at 0 (baseline), 60 days, and 90 days after compounding for suspensions made with raw powders, which were stored at 2ÅãC to 8ÅãC. The stability of tablets, which were stored at 2ÅãC to 8ÅãC and 20ÅãC to 25ÅãC, was assessed by measuring the percentage recovery at 0 (baseline), 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by ultraviolet high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions in the conditions tested. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.
- Clinical relevance in present day hormonal contraception. [Review]
- HMHorm Mol Biol Clin Investig 2018 Oct 26
- The contraceptive pill is an effective and very safe method to control pregnancies. It was developed 60 years ago, and despite that the composition has been the same since it was first developed (est...
The contraceptive pill is an effective and very safe method to control pregnancies. It was developed 60 years ago, and despite that the composition has been the same since it was first developed (estrogen and progestogen), over the years the concentration of ethinyl estradiol has been reduced to improve tolerability. Nevertheless, progestogens are the basic active agent of hormonal contraception. The mechanism of progestogens is a multimodal one and basically three modes of contraceptive action can be distinguished: (a) A strong antigonadotrophic action leading to the inhibition of ovulation. The necessary dosage of ovulation inhibition per day is a fixed dosage that is intrinsic to each progestogen and independent of the dosage of estrogen used or the partial activities of the progestogen or the mode of application. (b) Thickening of the cervical mucus to inhibit sperm penetration and (c) desynchronization of the endometrial changes necessary for implantation. The on the market available progestogens used for contraception are either used in combined hormonal contraceptives (in tablets, patches or vaginal rings) or as progestogen only contraceptives. Progestogen only contraceptives are available as daily oral preparations, monthly injections, implants (2-3 years) and intrauterine systems (IUS). Even the long-acting progestogens are highly effective in typical use and have a very low risk profile. According to their introduction into the market, progestogens in combined hormonal contraceptives, have been described as 1st, 2nd, 3rd and 4th generation progestogens. The different structures of progestogens are derivatives from testosterone, progesterone and spironolactone. These differences in the molecular structure determine pharmacodynamic and pharmacokinetic differential effects which contribute to the tolerability and additional beneficial or therapeutic effects whether used in combined oral contraceptive (COC) or as progestogen only drugs. These differences enhance the individual options for different patient profiles. The new development of polymers for vaginal rings allowed on the one hand, the improvement of the estrogen/progestogen combination in these rings especially regarding the comfort of use for women (e.g. avoiding the use of cold chains or packages with up to 6-month rings) and on the other hand, the development of progestogen only formulations. Another future development will be the introduction of new progestogen only pills that will provide effective contraceptive protection with more favorable bleeding patterns and a maintenance of ovulation inhibition after scheduled 24-h delays in pill intake than the existing progestogen only pill (POP) with desogestrel (DES).
- Cardiac expression of neutrophil gelatinase-associated lipocalin in a model of cancer cachexia-induced cardiomyopathy. [Journal Article]
- EHESC Heart Fail 2018 Oct 26
- CONCLUSIONS: Cancer cachexia induced increased levels of aldosterone and NGAL, contributing to worsening cardiac damage in cancer cachexia-induced cardiomyopathy. Spironolactone treatment may greatly attenuate cardiac dysfunction and lean mass atrophy associated with cancer cachexia.
- Nanoamorphous drug products - Design and development. [Journal Article]
- IJInt J Pharm 2018 Oct 22; 553(1-2):238-260
- Most of the recent drug compounds coming out of the drug discovery pipeline are labile (multiple polymorphs), and need to be developed into robust marketed oral drug formulations. There are only 22 o...
Most of the recent drug compounds coming out of the drug discovery pipeline are labile (multiple polymorphs), and need to be developed into robust marketed oral drug formulations. There are only 22 oral macroamorphous drug products approved by FDA and till date none approved oral nanoamorphous drug products. However, there are several oral nanoamorphous drug formulations (including both labile and non-labile drugs) being researched and a few of these are in the clinical trials. Due to the labile nature of these drug compounds, there is a need to utilize a controlled strategy for design and development of robust nanoamorphous drug formulations in order to prevent any physicochemical instability. The present research focuses on the use of a novel integrated critical process parameters and critical formulation parameters (iCPP-CFPs) DoE approach for the design and development of stable nanoamorphous spironolactone (BCS class II compound with eight polymorphic forms). There are possibilities of the interconversion of these polymorphic forms during processing (manufacturing nanoamorphous particles) and during storage. In the present study, polymorphic transitions (amorphous to crystalline and anhydrous to hydrate) were carefully monitored via orthogonal solid-state characterization tools. Significant polymorphic transitions were observed in the formulations stored at 40 °C/75% RH over six months, however the formulations stored at 4 °C were stable. The significant iCPP-CFPs (solvent-to-antisolvent ratio, drug concentration and inlet temperature of the spray dryer) were critically investigated for their influence on different CQAs (critical quality attributes). Solvent-to-antisolvent ratio and inlet temperature were identified to be the significant iCPP-CFPs. Particle size and total product yield were identified to be the significant CQAs. Lab-scale manufacturing of the spray dried nanoamorphous spironolactone resulted in a remarkably high total product yield (82.4 ± 3.91% w/w) with a uniform and homogenous particle size (244.2 ± 23.32 nm). Furthermore, the physicochemical attributes and the drug release criteria of the nanoamorphous spironolactone were compared with two marketed products (spironolactone tablets, USP 100 mg (Pfizer and Mylan)) and other in-house formulations. In addition, nanoamorphous spironolactone showed a significantly superior kinetic solubility/dissolution rate (10-fold) with a longer supersaturation time (∼6h) compared to the in-house formulations.
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- Two-year follow-up of mineralocorticoid receptor antagonists for chronic central serous chorioretinopathy. [Journal Article]
- BJBr J Ophthalmol 2018 Oct 24
- CONCLUSIONS: The visual and anatomical benefit of MRa treatment prolonged for 6 months or more in chronic, non-resolving CSC appeared to be maintained over a 24-month period. These results suggest that MRa can be proposed as an alternative therapy in severe CSC with advanced RPE alterations.