THE EFFECT OF DERIVATIVES OF DITHIOCARBAMOYLHYDRAZINE ON HORMONE EXCRETION IN POSTMENOPAUSAL WOMEN

1962 ◽  
Vol 25 (2) ◽  
pp. 221-231 ◽  
Author(s):  
E. T. BELL ◽  
J. B. BROWN ◽  
K. FOTHERBY ◽  
J. A. LORAINE ◽  
J. S. ROBSON
Keyword(s):  
Side Effects ◽  
Postmenopausal Women ◽  
Liver Damage ◽  
Adrenocortical Function ◽  
Human Pituitary ◽  
Dose Levels ◽  
Hormone Excretion ◽  
Derivatives Of

SUMMARY Estimations of human pituitary gonadotrophins (HPG), total 17-hydroxycorticosteroids, total 17-oxosteroids and oestrogens have been performed in seven hospitalized postmenopausal subjects receiving treatment with the dithiocarbamoylhydrazine derivatives Compound 22365 and Compound 33828 (Imperial Chemical Industries Ltd.). Both compounds were shown to be inhibitors of pituitary gonadotrophic function as indicated by urinary HPG assays; Compound 33828 was more active in this respect than Compound 22365. When Compound 22365 was administered to individual subjects at two different dose levels the time taken for urinary HPG levels to return to pretreatment values was longer in the case of the higher dose. Neither of the compounds studied produced any effect on adrenocortical function as judged by urinary assays of 17-hydroxycorticosteroids, 17-oxosteroids and oestrogens. Side effects were noted in two of the seven patients studied. In one subject with pre-existing liver damage it was necessary to stop treatment with Compound 22365 because of the development of mild jaundice.

Severe Isolated Prothrombin Deficiency : an Acquired State with Complete Recovery

1962 ◽  
Vol 08 (02) ◽  
pp. 221-234 ◽  
Author(s):  
Simon Karpatkin ◽  
G.I.C Ingram ◽  
John B. Graham
Keyword(s):  
Vitamin K ◽  
Liver Damage ◽  
Complete Recovery ◽  
Factor Vii ◽  
Natural Vitamin ◽  
Patient’S History ◽  
Derivatives Of

SummaryA 62 year old man acquired a temporary, virtually complete, deficiency of prothrombin as measured by both the Iowa and Oxford 2-stage methods. The etiology agent (or agents) is not known, but one of the drugs listed in Table 1 or an interaction between several was probably responsible. There was no evidence of an inhibitor, and factors I (fibrinogen), V (AcG), VII (SPCA), VIII (AHF), IX (PTC), X (Stuart), and XII (Hageman) were demonstrated to be normal. There were other evidences of mild liver damage and the prothrombin deficiency did not respond immediately to injections of natural vitamin K. Greatly prolonged clotting times but only moderately prolonged prothrombin times and partial thromboplastin times were observed. Bleeding was very severe into many tissues. Thromboplastin generation proceeded normally in the patient’s pro-thrombin-deficient plasma, despite the appearance of only a trace of thrombin. This patient’s history and clotting profile argue against the concept that factor VII (SPCA) and IX (PTC) are derivatives of prothrombin.

Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

1984 ◽  
Vol 51 (02) ◽  
pp. 248-253 ◽  
Author(s):  
R J Dupe ◽  
P D English ◽  
R A G Smith ◽  
J Green
Keyword(s):  
Pulmonary Embolism ◽  
Side Effects ◽  
Venous Thrombosis ◽  
Active Site ◽  
Acute Pulmonary Embolism ◽  
Quantitative Model ◽  
Beagle Dog ◽  
Thrombosis Model ◽  
Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

All-trans retinoic acid: tolerance and biologic effects in myelodysplastic syndrome.

1993 ◽  
Vol 11 (8) ◽  
pp. 1489-1495 ◽  
Author(s):  
R Kurzrock ◽  
E Estey ◽  
M Talpaz
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Myelodysplastic Syndrome ◽  
Acid Tolerance ◽  
Maximum Tolerated Dose ◽  
Significant Activity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Biologic Effects ◽  
Dose Levels

PURPOSE We conducted a study to evaluate the tolerance to and biologic effects of all-trans retinoic acid in patients with myelodysplastic syndrome. PATIENTS AND METHODS Thirty-nine patients with myelodysplastic syndrome were treated with oral all-trans retinoic acid for 6 weeks. Dose levels were 10, 25, 50, 100, 150, 200, and 250 mg/m2/d. At least three patients were treated on each dose level. RESULTS The most common side effects were mucocutaneous dryness and erythema, and hypertriglyceridemia. Dose-limiting side effects were diverse and included dermatitic problems, sensorineural hearing loss, headaches, nausea and vomiting, myalgias, and dyspnea. The maximum-tolerated dose was 150 mg/m2/d. Only one response was seen among 29 patients considered assessable for response. CONCLUSION All-trans retinoic acid can be safely administered to patients at doses up to 150 mg/m2/d for 6 weeks. However, as administered in this study, this compound does not appear to have significant activity in myelodysplastic syndromes.

scholarly journals Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

2019 ◽  
Vol 28 (1) ◽  
pp. 138-146
Author(s):  
Mustafa H. Ali Alsafi ◽  
Muthanna S. Farhan
Keyword(s):  
Side Effects ◽  
Mefenamic Acid ◽  
Paw Edema ◽  
Compound I ◽  
Reference Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Derivatives Of ◽  
Cox 1 ◽  
Inflammatory Effect

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect.

scholarly journals Al-Qur�an dan Sains?(Bukti Kebenaran dalam Kasus Propolis Madu)

2014 ◽  
Vol 12 (1) ◽  
Author(s):  
MF. Zenrif Dan Erna Susanti
Keyword(s):  
Free Radicals ◽  
Liver Damage ◽  
Rhodamine B ◽  
Therapy Group ◽  
Carcinogenic Effect ◽  
Treatment Groups ◽  
Group 3 ◽  
Group 2 ◽  
Dose Levels ◽  
Rhodamin B

Exposure free radicals in the activity of this life can not be avoided, included exposure free radicals from food additive espesifically Rhodamine B. Carcinogenic effect of Rhodamin B can be caused by Poly Aromatic Hydrocarbons structure that are destructive to the liver as metabolism organ. The purpose of this study was to prove the antioxidant activity of Honey Propolis against liver damage caused by exposure of Rhodamine B as free radical sources. Indicator of liver damage can be indicated by MDA, a marker of oxidative stress that occurs in these organs. The methode was used experimental methode, with seven treatment groups, namely: (1) normal group, (2) the induction of Rhodamin B without propolis therapy group, (3) the induction of Rhodamin B with Honey Propolis therapy with three dose levels are 350 mg, 700 mg and 1050 mg that are given at intervals of two hours after the administration of Rhodamine B (4) Honey Propolis therapy groups are given at interval of 1 week aftertheadministrationof RhodamineBwiththreedoselevels.MDAlevelsweremeasuredbyTBARS method. The results showed that the levels of Malondialdehyde declined steadily in the group treated with honey propolis to less than control groups. There are significant differences in MDA levels between the treatment groups Honey Propolis therapy (p = 0.034, p <0.05). Based on these results, it can be concluded that Honey propolis dose 700 mg act as therapeutic agent in liver damage due to exposure of Rhodamine B significantly.The results ofthis studyprove thetruth ofthe Quraninthe QS. Al-Nahl (16): 69of thewonders ofhoneyin preventingliver damagedue toexposure tohazardous substancesin food.

An Open Study of Two Dose Levels of ‘Vivalan’ (Viloxazine Hydrochloride ICI 58 834) in Depression in General Practice

1974 ◽  
Vol 2 (4) ◽  
pp. 253-259 ◽  
Author(s):  
P F C Bayliss ◽  
J W Harcup ◽  
M Mayer ◽  
R Million ◽  
J E Murphy ◽  
...  
Keyword(s):  
General Practice ◽  
Depressive Symptoms ◽  
Side Effects ◽  
Side Effect ◽  
Open Study ◽  
Anxiety Symptoms ◽  
High Dose ◽  
Dose Levels

Forty-eight mild to moderate depressives were treated by six genera practitioners with a chemically novel anti-depressant, ‘Vivalan’ (viloxazine hydrochloride, ICI 58 834). Twenty-five patients took 150 mg/day in three divided doses, and twenty-three took 200 mg/day in two divided doses, each for twenty-one days. The severity of both the depressive symptoms and the anxiety symptoms showed a statistically highly significant reduction over the duration of the study. There was no difference between the efficacy of the two dose levels. Viloxazine was generally well tolerated and there was no difference between the two dose levels as far as side-effects or withdrawals were concerned. The usual sedative and anti-cholinergic side-effects of the tricyclic anti-depressants were virtually absent. The only side-effect seen was a transient upper gastro-intestinal disturbance. It was commoner at the high dose but not significantly so. It is concluded that viloxazine hydrochloride appears to be an effective anti-depressant in this type of patient and produces little or no sedative or anti-cholinergic side-effects. Either 150 mg/day or 200 mg/day would seem a reasonable dose to use in general practice.

Correction of pyrimidine derivatives of immunologic activity of the organism and external respiration function for prevention of the lingering course of acute pneumonia

1993 ◽  
Vol 74 (3) ◽  
pp. 193-197
Author(s):  
Yu. D. Slabnov ◽  
D. A. Valimukhametova ◽  
A. P. Tsibulkin ◽  
R. F. Khamitov
Keyword(s):  
Side Effects ◽  
Combined Treatment ◽  
External Respiration ◽  
Pyrimidine Derivatives ◽  
Acute Pneumonia ◽  
Cellular And Humoral Immunity ◽  
Immunologic Activity ◽  
Derivatives Of ◽  
Respiration Function ◽  
Stabilization Period

The effect of xymedon on immunologic indices and external respiration function in combined treatment of patients with acute pnemonia is studied. The use of xymedon in the presence of basis therapy in patients with lingering pneumonia with reduced immunologic reactivity exerts a stimulating effect on the indices of cellular and humoral immunity. This effect is revealed in the stabilization period of pneumonia accompanied by positive clinicoroentgenologic shifts, provides a higher increase of the indices of external respiration function, reduces the terms of recovery of patients. Xymedon does not cause side effects. The drug may be recommended for a wider use in the clinic in patients with unspecific diseases of the lungs.

Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer.

1988 ◽  
Vol 6 (5) ◽  
pp. 825-831 ◽  
Author(s):  
J N Ingle ◽  
D I Twito ◽  
D J Schaid ◽  
S A Cullinan ◽  
J E Krook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Metastatic Breast Cancer ◽  
Side Effects ◽  
Postmenopausal Women ◽  
Randomized Clinical Trial ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
Rank Test ◽  
Breast Cancer Patients

A randomized clinical trial was performed to determine if combination hormonal therapy with tamoxifen (TAM) and fluoxymesterone (FLU) was more efficacious than TAM alone for the treatment of postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 TAM patients (42%) and 63 of 119 TAM plus FLU patients (53%) (one-sided P = .05). Time to disease progression distributions were better for TAM plus FLU (median, 350 days v 199 days), but the log rank test only approached statistical significance (one-sided P = .07). Duration of response and survival distributions were similar between the two treatment arms. Toxicities, in terms of androgenic side effects, were greater on the TAM plus FLU regimen. Fifty-two patients are evaluable for response with FLU following TAM and 21 (40%) have achieved a response. We conclude that the advantages in terms of response rate and time to progression observed with TAM plus FLU probably represent a biological effect, but are not of sufficient magnitude to justify the routine clinical use of this combination given the lack of survival advantage and side effects encountered.

scholarly journals Schistosoma mansoni: preclinical studies with 9-acridanone-hydrazones in Cebus monkeys experimentally infected

1991 ◽  
Vol 33 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Paulo Marcos Zech Coelho ◽  
Leógenes Horácio Pereira
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Schistosoma Mansoni ◽  
Drug Administration ◽  
Worm Burden ◽  
Preclinical Studies ◽  
Cebus Monkeys ◽  
Derivatives Of

Derivatives of acridine (9-Acridanone-hydrazones) were tested in Cebus monkeys experimentally infected with Schistosoma mansoni, at the dosages of 50, 25, and 12.5 mg/kg (p.o., single dose). At least, four compounds seemed to be very promising, promoting alterations in the oogram and reducing the worm burden drastically, even at the lowest dose (12.5 mg/kg). No side effects could be detected after drug administration.

Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1

2016 ◽  
Vol 43 (1-2) ◽  
pp. 45-58 ◽  
Author(s):  
Zdenka Kristofikova ◽  
Jan Ricny ◽  
Ondrej Soukup ◽  
Jan Korabecny ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Side Effects ◽  
Amyloid Β ◽  
Acetylcholinesterase Inhibitors ◽  
Side Chain ◽  
Choline Transporter ◽  
Disease Therapy ◽  
Cortical Membranes ◽  
Derivatives Of

Background: Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. Methods: We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Results: Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. Conclusion: The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research.

Sign in / Sign up

Export Citation Format

Share Document