Effect of Short-Term and Long-Term Treatment with a Steroidal Oral Contraceptive on the Intestinal Absorption of Nutrients in vitro in Female Rats

ABSTRACT The influence of short-term and long-term treatment with gonadal hormones on the response to calcitonin was investigated in the rat. Oestrogen-treatment, short-term as well as long-term, resulted in a reduced responsiveness to calcitonin. Long-term treatment with androgens enhanced the hypocalcaemic effect of calcitonin in castrated rats of either sex, but reduced the effect in intact animals. No sex differences could be registered in the sensitivity to calcitonin, when intact animals were compared according to age, while marked differences were observed, when the animals were compared according to weight. There was a linear decrease in the response to calcitonin with increasing age in rats of both sexes. An intraperitoneal calcium load was followed by an acute rise in the serum calcium levels. The adult animals counteracted the hypercalcaemia more slowly than the young ones. Significant differences also occurred between male and female rats, the rise in the serum calcium concentration being much more pronounced in the latter group. The hypocalcaemic activity of thyroid tissue from rats of both sexes and of various ages showed considerable variations, but no differences correlated to age or sex.

Download Full-text

Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats

AJP Renal Physiology ◽

10.1152/ajprenal.90272.2008 ◽

2009 ◽

Vol 296 (3) ◽

pp. F605-F613 ◽

Cited By ~ 41

Author(s):

Francisco J. Mendoza ◽

Ignacio Lopez ◽

Rocio Canalejo ◽

Yolanda Almaden ◽

David Martin ◽

...

Keyword(s):

Cell Proliferation ◽

Term Treatment ◽

Parathyroid Cell ◽

Calcium Sensing Receptor ◽

Short Term ◽

Calcium Sensing ◽

Long Term Treatment ◽

Acute Increase

To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the short-term protocol. A significant increase in CaSR mRNA (% vs. β-actin) was detected in rats treated with both calcitriol (1.60 ± 0.30) and AMG 641 (1.66 ± 0.25) for 13 days ( P = 0.01 vs. 5/6 Nx+vehicle, 0.89 ± 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 ± 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 ± 0.33, P < 0.001) showed increased expression of CaSR mRNA, whereas the combination (1.81 ± 0.20) produced no additional benefit. AMG 641 also increased CaSR mRNA expression in vitro. Changes in VDR mRNA paralleled those of CaSR mRNA. In the long-term treatment, both AMG 641 (0.87 ± 0.14) and calcitriol (0.99 ± 0.12) increased VDR mRNA ( P < 0.05 vs. 5/6 Nx+vehicle, 0.49 ± 0.10), and the increase was more accentuated when the drugs were combined (1.49 ± 0.45). In the short-term protocol, only treatment with AMG 641, alone (1.52 ± 0.41) or combined with calcitriol (1.86 ± 0.24), increased VDR mRNA. In conclusion, our results demonstrate an acute increase in CaSR mRNA and VDR mRNA in the parathyroid glands of uremic rats treated with AMG 641, in which cell proliferation was uncontrolled, thus supporting a direct effect of calcimimetics on CaSR and VDR expression by hyperplastic parathyroid cells.

Download Full-text

Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma

Neuro-Oncology ◽

10.1093/neuonc/noz060 ◽

2019 ◽

Vol 21 (7) ◽

pp. 890-900 ◽

Cited By ~ 4

Author(s):

Jubayer A Hossain ◽

Md A Latif ◽

Lars A R Ystaas ◽

Sandra Ninzima ◽

Kristoffer Riecken ◽

...

Keyword(s):

Gene Therapy ◽

Tumor Cells ◽

Suicide Gene ◽

Term Treatment ◽

Suicide Gene Therapy ◽

Short Term ◽

Short Term Treatment ◽

Long Term Treatment

Abstract Background Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when replication-defective vectors were used. We previously showed that a substantial fraction of herpes simplex virus thymidine kinase (HSV-TK) transduced tumor cells survive ganciclovir (GCV) treatment in an orthotopic glioblastoma (GBM) xenograft model. Here we analyzed whether these TK+ tumor cells are still sensitive to prodrug treatment and whether prolonged prodrug treatment can enhance treatment efficacy. Methods Glioma cells positive for TK and green fluorescent protein (GFP) were sorted from xenograft tumors recurring after suicide gene therapy, and their sensitivity to GCV was tested in vitro. GBM xenografts were treated with HSV-TK/GCV, HSV-TK/valganciclovir (valGCV), or HSV-TK/valGCV + erlotinib. Tumor growth was analyzed by MRI, and survival as well as morphological and molecular changes were assessed. Results TK-GFP+ tumor cells from recurrent xenograft tumors retained sensitivity to GCV in vitro. Importantly, a prolonged period (3 mo) of prodrug administration with valganciclovir (valGCV) resulted in a significant survival advantage compared with short-term (3 wk) application of GCV. Recurrent tumors from the treatment groups were more invasive and less angiogenic compared with primary tumors and showed significant upregulation of epidermal growth factor receptor (EGFR) expression. However, double treatment with the EGFR inhibitor erlotinib did not increase therapeutic efficacy. Conclusion Long-term treatment with valGCV should be considered as a replacement for short-term treatment with GCV in clinical trials of HSV-TK mediated suicide gene therapy.

Download Full-text

A retrospective, observational, single center study of gonadotropin-releasing hormone agonist protocols at the Reproductive Center of Farah Hospital in Jordan

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20193402 ◽

2019 ◽

Vol 7 (8) ◽

pp. 3103

Author(s):

Zaid Kilani ◽

Mohammad Shaban

Keyword(s):

Term Treatment ◽

Gonadotropin Releasing Hormone ◽

Clinical Pregnancy ◽

Short Term ◽

Short Term Treatment ◽

Releasing Hormone ◽

Long Term Treatment ◽

Group A

Background: Data on infertility and in vitro fertilization (IVF) are incomplete and uncertain in Jordan and worldwide because of difficulties in evaluating infertility in the general population. This study aimed at comparing the effectiveness of the gonadotropin-releasing hormone agonists (GnRH-a) long and short protocols as part of IVF or intracytoplasmic sperm injection.Methods: This observational, retrospective, comparative, longitudinal study was conducted in a reproductive center in Jordan. It reviewed data charts from women who took GnRH-a for IVF, from 2010 to 2013. These were categorized in Group A (long-term GnRH-a: single 3.75 mg-monthly injection) or Group B (short-term GnRH-a: multiple daily 0.1 mg injections). The primary endpoint was the rate of ongoing clinical pregnancy (number of pregnancies/number of women) and live birth rate in fresh cycle/protocols.Results: Out of 1,946 eligible women, 471 underwent the long-term treatment of GnRH-a administration and 1,523 the short-term treatment. The women’s mean age was 29.61±3.80 years old. Out of the 471 women in Group A, 216 (45.9%) women had ongoing clinical pregnancy, of whom 69 (31.9%) had live births. In the short-protocol group, 485 (31.8%) women had ongoing clinical pregnancy, of whom 133 (27.4%) had live births.Conclusions: GnRH-a long protocol is more effective than the short protocol regardless of the agonist formulation used in subfertile women/men who underwent IVF/ intracytoplasmic sperm injection.

Download Full-text

Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells

Tumor Biology ◽

10.3233/tub-211515 ◽

2021 ◽

Vol 43 (1) ◽

pp. 327-340

Author(s):

Tales Henrique Andrade da Mota ◽

Ana Flávia Reis Guimarães ◽

Amandda Évelin Silva de Carvalho ◽

Felipe Saldanha- de Araujo ◽

Giselle Pinto de Faria Lopes ◽

...

Keyword(s):

Cell Cycle ◽

Treatment Resistance ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

Telomerase Inhibitor ◽

Long Term Treatment ◽

Short And Long Term

BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.

Download Full-text

Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro

Molecules ◽

10.3390/molecules26092607 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2607

Author(s):

Yuzhen Gao ◽

Jingjing Cao ◽

Pan Xing ◽

Ralf Altmeyer ◽

Youming Zhang

Keyword(s):

Respiratory Syncytial Virus ◽

Confidence Interval ◽

The Elderly ◽

Term Treatment ◽

Fusion Inhibitors ◽

Long Term Treatment ◽

Statistical Program ◽

Syncytial Virus

Respiratory syncytial virus (RSV) is a major pathogen that causes severe lower respiratory tract infection in infants, the elderly and the immunocompromised worldwide. At present no approved specific drugs or vaccines are available to treat this pathogen. Recently, several promising candidates targeting RSV entry and multiplication steps are under investigation. However, it is possible to lead to drug resistance under the long-term treatment. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). The statistical program MacSynergy II was employed to determine synergism, additivity or antagonism between drugs. From the result, we found that combinations of ALS8176 and Ziresovir or GS5806 exhibit additive effects against RSV in vitro, with interaction volume of 50 µM2% and 31 µM2% at 95% confidence interval, respectively. On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from −50 µM2 % to −176 µM2 % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations.

Download Full-text

Long-Term Treatment with Pivmecillinam in Patients with Recurrent Bacteriuria

Journal of International Medical Research ◽

10.1177/030006058201000307 ◽

1982 ◽

Vol 10 (3) ◽

pp. 179-182

Author(s):

B Bresky ◽

K Lincoln

Keyword(s):

Escherichia Coli ◽

Adverse Effect ◽

Renal Function ◽

Term Treatment ◽

The Body ◽

End Of Treatment ◽

Long Term Treatment ◽

Tract Infections

Thirty out-patients with chronic recurrent urinary tract infections, who had failed to respond to 10 days treatment with either pivmecillinam and/or amoxycillin, received a 3-month course of pivmecillinam at a dose of 200 mg, three times daily. Twenty-seven patients had bacteriuria due to Enterobacteriaceae, mainly Escherichia coli, sensitive to mecillinam in vitro. Pivmecillinam eradicated all the initial urinary pathogens. Reinfections occurred during treatment in three patients, who remained asymptomatic. Four subjects complained of gastro-intestinal side-effects, and therapy was withdrawn in three instances. Another three patients described unusual adverse events towards the end of the course of treatment, described as an odd sensation in the body and a desire for salt. The sensation disappeared a few days after the end of treatment. Treatment with pivmecillinam had no adverse effect on haematopoietic, hepatic or renal function.

Download Full-text

Fluvoxamine in the Treatment of Trichotillomania: An 8-Week, Open-Label Study

CNS Spectrums ◽

10.1017/s1092852900006520 ◽

1998 ◽

Vol 3 (9) ◽

pp. 64-71 ◽

Cited By ~ 4

Author(s):

Gary A. Christenson ◽

Scott J. Crow ◽

James E. Mitchell ◽

Thomas B. Mackenzie ◽

Ross D. Crosby ◽

...

Keyword(s):

Treatment Response ◽

Term Treatment ◽

Hair Pulling ◽

Short Term ◽

Open Label ◽

Short Term Treatment ◽

Open Label Study ◽

Label Study ◽

Long Term Treatment

AbstractThis short-term, open-label study investigates short- and long-term effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for the treatment of trichotillomania (TTM). Additionally, this study aimed to test the hypothesis that the presence of hair pulling compulsiveness is predictive of SSRI response. Nineteen subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, (DSM-III-R) criteria for TTM were treated with fluvoxamine at doses up to 300 mg/day. Random regression analysis of change across time for patients who completed the study (n=14) and those who dropped out (n=5) revealed statistically significant improvements in Physician Rating Scale, hair-pulling episodes, Trichotillomania Impairment Scale, and Trichotillomania Symptom Severity Scale, but not in estimated amount of hair pulled. In addition, the percentage of patients' focused or compulsive hair-pulling symptoms was predictive of treatment response. Unfortunately, all three subjects who entered long-term treatment displayed substantial movement back toward baseline by the end of 6 months. We concluded that fluvoxamine produces moderate reductions in symptoms during the short-term treatment of TTM and that the presence of focused or compulsive hair pulling may be predictive of treatment response. However, responses may be short lived when treatment is extended.

Download Full-text

Beneficial effects of long-term treatment with beta-adrenergic blocker on depressed heart function of female rats

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2008.02.251 ◽

2008 ◽

Vol 44 (4) ◽

pp. 816

Author(s):

Aytac Seymen ◽

Erkan Tuncay ◽

Hakan Gurdal ◽

Belma Turan

Keyword(s):

Heart Function ◽

Term Treatment ◽

Female Rats ◽

Beta Adrenergic ◽

Beneficial Effects ◽

Long Term Treatment ◽

Adrenergic Blocker

Download Full-text

Nonmedical Interventions for Schizophrenia: A Review of Diet, Exercise and Social Roles

10.31234/osf.io/8fm32 ◽

2020 ◽

Author(s):

Daniel S. Helman

Keyword(s):

Term Treatment ◽

Physical Processes ◽

Dietary Interventions ◽

Short Term ◽

Alternative Interventions ◽

Social Interventions ◽

General Utility ◽

Long Term Treatment ◽

Abnormal Lipid Metabolism

Schizophrenia is a major mental illness with a disease course that is influenced by lifestyle. The risk-benefit ratio for alternative interventions is more favorable than for antipsychotics in long-term treatment. Dietary interventions may target autoimmune features, vitamin or mineral deficiencies, abnormal lipid metabolism, gluten sensitivity or others. Examples of interventions involving diet, physical activity or physical processes, or social interventions including talk therapy exist in the literature. Notwithstanding, the general utility of these types of interventions remains inconclusive, awaiting long-term randomized trials. A perspective that separates the cause of the disease from its symptoms may be helpful in treatment planning and is warranted to distinguish between short-term and long-term recovery goals.

Download Full-text