scholarly journals Study of chronic toxicity of the GB-115 drug formulation

Author(s):  
A. V. Sorokina ◽  
S. V. Alekseeva ◽  
I. A. Miroshkina ◽  
V. V. Zabrodina ◽  
L. G. Kolik ◽  
...  

The results of the study of chronic toxicity of the drug formulation of anxiolytic GB-115 are presented. The novel dipeptide in the form of a tablet mass was administered daily orally for 6 months to outbred rats and rabbits of the chinchilla breed at a dose of 1 mg/kg corresponding to the therapeutic and 50 mg/kg exceeding the therapeutic dose by 50 times. Clinical, laboratory and pathohistological studies performed in accordance with the General Protocol demonstrated the absence of toxic effects of the GB-115 drug formulation. The exception was the reversible changes in the coagulation activity in rats and rabbits, which were not associated with the dose of the GB-115 solid dosage from.

Author(s):  
A. V. Sorokina ◽  
S. V. Alekseeva ◽  
I. A. Miroshkina ◽  
K. S. Kachalov ◽  
A. D. Zaharov ◽  
...  

Presents results of a study of subchronic toxicity of homeopathic drug Dantinorm Baby in finished dosage form. The drug in the form of a ready solution was administered daily orally for one month to outbred rats Infanta and chinchilla rabbits at a dose of 0.3 ml/kg, corresponding to the therapeutic, and 3 ml/kg, exceeding the therapeutic dose 10 times. Clinical, laboratory and histopathological studies performed in accordance with the General Protocol, showed no toxic effects of homeopathic preparation of Dantinorm Baby. The totality of the obtained data of the subchronic experiment indicates that there are no obstacles to the clinical study of the drug Dantinorm Baby in the range of therapeutic dosages.


1962 ◽  
Vol 40 (1) ◽  
pp. 1685-1692
Author(s):  
Eldon M. Boyd ◽  
Dorothy A. Mulrooney ◽  
Everett J. Sargeant

Young, adult albino mice and rats became more susceptible to the acute and chronic toxic effects of benzylpenicillin after they had been fed vitamin A deficient test diet, U.S.P. XIV, for about 1 month. At and after this interval, there occurred a significant increase in the percentage mortality from a single oral or subcutaneous LD50 of benzylpenicillin in mice and the chronic toxicity of a daily oral 0.1 L-LD50 of benzylpenicillin was augmented in rats. Replacement of vitamin A, in the deficient diet or by daily intramuscular injection, did not affect the increased susceptibility to benzylpenicillin toxicity. A dietary supplement containing nine other vitamins was also without effect. Change in diet alone was not a factor since rats did not become appreciably more susceptible to the toxic effects of a daily oral 0.1 L-LD50 of benzylpenicillin when their diet was changed from a standard laboratory chow to a rachitogenic test diet. Some unknown factor or factors in vitamin A deficient test diet, U.S.P. XIV, therefore, made the animals more susceptible to the toxic effects of benzylpenicillin.


Author(s):  
Sally Thirkettle ◽  
Joanne Russell ◽  
Sarah Wilson ◽  
Tasneem Ganijee ◽  
Samar Kulkarni ◽  
...  

Background The novel daratumumab immunotherapy is a human IgG1 kappa antibody targeted against CD38, which is almost universally expressed on myeloma plasma cells. Daratumumab has efficacy in clinical trials for the treatment of multiple myeloma; however, it complicates laboratory monitoring of the serological response to treatment, as it is detected by serum electrophoresis and/or immunofixation. Methods Laboratory reports of electrophoresis patterns serially performed in a single laboratory of six patients with relapsed multiple myeloma receiving daratumumab therapy as part a clinical trial were reviewed retrospectively. Results Post administration of daratumumab therapy, an additional band was visible by serum electrophoresis, migrating to the mid-gamma region, which was confirmed as IgG kappa by immunofixation. In five out of the six patients, this band was quantified at <2.0 g/L. For one patient, this band co-migrated with the patient’s disease paraprotein band, so both bands were quantified together. The appearance of an apparent second paraprotein band while receiving treatment for multiple myeloma can cause anxiety for patients, confusion for healthcare workers and may also underestimate complete remission rates. Conclusions The clinical laboratory must be aware of the interference of daratumumab in serum electrophoresis. Effective communication between clinicians and the laboratory is essential for the production of clinically valuable, non-misleading reports for these patients.


2020 ◽  
pp. 1-5
Author(s):  
Akshay Khatri ◽  
Esti Charlap ◽  
Angela Kim

<b><i>Introduction:</i></b> The novel severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) virus has led to the ongoing Coronavirus disease 2019 (COVID-19) disease pandemic. There are increasing reports of extrapulmonary clinical features of COVID-19, either as initial presentations or sequelae of disease. We report a patient diagnosed with subacute thyroiditis precipitated by COVID-19 infection, as well as review the literature of similar cases. <b><i>Case Presentation:</i></b> A 41-year-old female with no significant personal or family history of endocrinologic disorders presented with clinical features of thyroiditis that began after COVID-19 infection. Clinical, laboratory, and radiologic findings were indicative of subacute thyroiditis. Workup for potential triggers other than SARS-CoV-2 was negative. <b><i>Discussion/Conclusion:</i></b> We compared the clinical and diagnostic findings of our patient with other well-documented cases of subacute thyroiditis presumed to be triggered by SARS-CoV-2 viral infection. We also reviewed the literature related to the potential mechanisms leading to thyroiditis. Clinicians must be aware of the possibility of thyroid dysfunction after COVID-19 infection. Early recognition and timely anti-inflammatory therapy help in successful management.


2020 ◽  
pp. 002198942095212
Author(s):  
Shazia Rahman

Nadeem Aslam’s novel The Blind Man’s Garden (2013) describes the post-9/11 international conflict in Afghanistan and its effect on a Pakistani character named Mikal, who ends up imprisoned and tortured by both Afghan warlords and American soldiers and remains especially cognizant of the multispecies nature of our world. In this article, I argue that even though the novel presents the toxic effects of hegemonic masculinity by depicting war, it also provides an alternative. In particular, Mikal, with his non-hierarchical response to the War on Terror, gender equity, and nonhuman animals, models much-needed helpful rather than harmful behaviours. I call this stance postcolonial ecomasculinity and link it to the way in which a snow leopard cub influences Mikal’s decision to rescue a US soldier by risking his own life and wellbeing. Even though the US soldier also befriends the same snow leopard cub, his hegemonic masculine desire for dominance makes it difficult for him to overcome his ethnocentrism. Similarly, Aslam’s novel depicts Rohan, who identifies with and appreciates nonhuman birds and trees, but because of his patriarchal privilege cannot see the ways in which women are also oppressed. As the novel ends, its women characters provide hope for Rohan, the blind man, to navigate through the garden, which is Pakistan, using a rope walk to connect Rohan to the plants and trees in the garden. These connections are symbolic of lessons in egalitarian masculinity, teaching not only Rohan but also two young boys how to live without domination and violence. As a result, we are left with images of pathways which broaden our vision of masculinity beyond the stereotypical.


Author(s):  
Benny Antony ◽  
Merina Benny ◽  
Binu T. Kuruvilla ◽  
Nishant Kumar Gupta ◽  
Anu Sebastian ◽  
...  

Objective: The objective of the present study was to evaluate the acute and sub-chronic (90 d; repeated dose) toxicity of Withania somnifera (ashwagandha) extract in rats.Methods: The acute toxicity was evaluated as per OECD (Organisation for Economic Co-operation and Development) guidelines 423. Purified ashwagandha extract (PAE) was fed at 2000 mg/kg body weight (bw) to overnight fasted female rats. The animals were observed daily for clinical signs of abnormality/mortality. After 14 d, animals were sacrificed and gross pathological changes were recorded. Sub-chronic toxicity of PAE was studied by feeding the extract at 100, 500 and 1000 mg/kg bw daily to rats as per OECD guidelines 408. After 90 d feeding, heamatological and biochemical parameters of treated rats were compared with control animals. Histopathology of all the major organs was also studied.Results: In the acute toxicity study, no mortality or clinical signs of toxicity were observed in any of the animals at maximum recommended dose level of 2000 mg/kg bw; therefore the LD50 is>2000 mg/kg bw in rats. The repeated administration of PAE for 90 d in rats at the maximum dose level of 1000 mg/kg bw did not induce any observable toxic effects, when compared to its corresponding control animals. The hematology and biochemistry profile of treated rats was similar to control animals and difference was non-significant (p>0.05). The histopathology of major organs of all the control and treated animals was normal. In this study the NOAEL (No Observed Adverse Effect Level) was calculated as 1000 mg/kg bw daily for rats.Conclusion: The present study clearly indicates that PAE does not have any toxic effects in animals at the dose evaluated as evidenced by acute and sub chronic toxicity studies in rats.


1991 ◽  
Vol 274 (2) ◽  
pp. 611-614 ◽  
Author(s):  
E J Griffiths ◽  
A P Halestrap

The Ki values of cyclosporins A, G and H for the peptidyl-prolyl cis-trans isomerase (PPIase) of liver and heart mitochondria are about 2, 20 and 500 nM respectively. This parallels their profile as inhibitors of non-specific pore opening of mitochondria induced by supraphysiological Ca2+ concentrations. The novel immunosuppressant FK-506 gave little inhibition of either process at 5 microM. These data support our previous hypothesis [Halestrap & Davidson (1990) Biochem. J. 268, 153-160] that pore opening involves an interaction between matrix PPIase and the adenine nucleotide translocase. It is suggested that this model may help to clarify the mechanism of action of cyclosporin as an immunosuppressant and its toxic effects on the liver and kidney following prolonged therapy.


Pharmaceutics ◽  
2012 ◽  
Vol 4 (4) ◽  
pp. 531-550 ◽  
Author(s):  
Svetlana Ibrić ◽  
Jelena Djuriš ◽  
Jelena Parojčić ◽  
Zorica Djurić

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.


2012 ◽  
Vol 10 (9) ◽  
pp. 1026-1034 ◽  
Author(s):  
Gemma Arjó ◽  
Teresa Capell ◽  
Xavier Matias-Guiu ◽  
Changfu Zhu ◽  
Paul Christou ◽  
...  

2005 ◽  
Vol 10 (suppl a) ◽  
pp. 23A-26A ◽  
Author(s):  
Pierre Beaulieu

The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.


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