SPECIAL PROBLEMS IN TOXICITY TESTING OF LONG ACTING DEPOT CONTRACEPTIVES

1974 ◽  
Vol 77 (1_Suppla) ◽  
pp. S315-S354 ◽  
Author(s):  
F. Neumann ◽  
R. von Berswordt-Wallrabe ◽  
W. Elger ◽  
K.-J. Gräf ◽  
S. H. Hasan ◽  
...  
Keyword(s):  
Biological Effects ◽  
Histological Finding ◽  
Toxicity Testing ◽  
Prolactin Secretion ◽  
List Type ◽  
Human Species ◽  
Prolactin Plasma Level ◽  
Human Use ◽  
Long Acting ◽  
Reproductive Processes

ABSTRACT Two types of so-called "depot contraceptives", long-acting steroids which are of interest for human use, were studied in animals. Norethisterone oenanthate, mainly gestagenic in the human and other species, turned out to be predominantly oestrogenic in rats. This oestrogenicity caused indirectly, via an enhanced hypophysial prolactin secretion, the well-known hypophysial and mammary tumours in rats. Another synthetic gestagen, 4,6-dichloro- 17- acetoxy- 16α-methyl-4,6-pregnadiene-3,20-dione, which might be considered in its biological actions similar to preparations containing chlormadinone acetate or medroxy-progesterone acetate, induced no signs of oestrogenicity in dogs. It is surmised that its gestagenic influence indirectly, and probaby, via an enhanced hypophysial prolactin secretion caused "mammary nodules" in this "non-rodent" species. These studies have born out mainly two facts: A synthetic steroid, norethisterone oenanthate, exerted different biological effects in different species: it was a gestagen in the rabbit, whereas in rats, its predominant influence was oestrogenic. The hypophysial prolactin secretion was enhanced in various species by different mechanisms: in rats, the oestrogenicity caused an increased prolactin plasma level, whereas in dogs, a gestagen with obviously no inherent oestrogenicity, 4,6-dichloro-17-acetoxy-16α-methyl-4,6-pregnadiene-3,20-dione, converted the histological appearance of the anterior pituitary into a condition with a greatly increased number of eosinophils. This histological finding was interpreted as an indicator for a hypersecretion of prolactin. Hence, animal work with "gestagens" has only limited predictive value with respect to their possible effects in the human species. Therefore, inflexible recommendations are not helpful in solving the safety problem of long-acting steroids which affect primarily reproductive processes.

scholarly journals Pasireotide in an insulin-requiring diabetic acromegalic patient without worsening of hyperglycemia

2017 ◽  
Vol 2017 ◽  
Author(s):  
Murray B Gordon ◽  
Kellie L Spiller
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
List Type ◽  
Effective Treatment Option ◽  
Patients With Diabetes ◽  
Long Acting ◽  
Learning Points

Summary Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient’s antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin. Learning points Long-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide. Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled. Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

2021 ◽  
Vol 19 ◽  
Author(s):  
Alex B. Speers ◽  
Kadine A. Cabey ◽  
Amala Soumyanath ◽  
Kirsten M. Wright
Keyword(s):  
Animal Studies ◽  
Withania Somnifera ◽  
Biological Effects ◽  
Leaf Extracts ◽  
Active Compounds ◽  
Symptoms Of Depression ◽  
Human Use ◽  
Preclinical And Clinical Studies ◽  
Anxiety Depression ◽  
Neuropsychiatric Conditions

Background: Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in public use worldwide due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders. Objective: This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia. Methods: Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases. Results: WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS. Conclusion: While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage from treating neuropsychiatric conditions. WS generally appears safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.

scholarly journals P59 Assessing medicines for safe use in paediatrics

2020 ◽  
Vol 105 (9) ◽  
pp. e37.1-e37
Author(s):  
Mary Worrall ◽  
Anne Fitzpatrick
Keyword(s):  
European Commission ◽  
Assessment Tool ◽  
New Products ◽  
Daily Intake ◽  
European Medicines Agency ◽  
List Type ◽  
Medicinal Products ◽  
Pharmaceutical Development ◽  
Human Use ◽  
Paediatric Medicines

AimThis service review aimed to reassess and upgrade the ‘New Products Assessment Form’ and to develop an assessment tool in line with European regulations governing paediatric medicines. Many medicinal products routinely used to treat the paediatric population have not been studied or authorised for paediatric use, which means there is widespread unlicensed and ‘off-label’ use of medicines. Medicines deemed safe in adult formulations may not be appropriate for paediatric patients. Medicines must therefore be carefully selected based on agreed criteria including, but not limited to: licensing, excipients, administration, labelling, similarity to other products, safety and handling.MethodA literature review was conducted. Guidance, information, and advice was sought from other healthcare institutions, and European guidelines and directives informing current practise around excipients in paediatric medicines. Pharmacy colleagues were consulted during the development of the tool, and an accessible assessment tool was completed for use in a tertiary paediatric hospital.1–4ResultsThis is the first comprehensive ‘New Products Assessment Form’ in the hospital which complies with the European Medicines Agency (EMA) directives governing excipients in paediatric medicines. The document highlights clearly potential issues and risks associated with product excipients, licensing status, warning label guidance and allows for recording of rationale for the selection of medicines. The ‘New Products Assessment Form’ is intended to highlight potential issues associated with excipients and their associated acceptable daily intake (ADI), but it will also highlight other risks associated with medicines used in paediatrics e.g. inadequate labelling, translation requirements for foreign products, sound-alike/look-alike products, safety and handling, and others.ConclusionThis revised assessment tool has been approved for use in the hospital pharmacy. It will be made available in hospital and community pharmacies on request. Use of the tool should be monitored and audited.ReferencesAnnex to the European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’ (SANTE-2017-11668). https://www.ema.europa.eu/en/documents/scientific-guideline/annex-european-commission-guideline-excipients-labelling-package-leaflet-medicinal-products-human_en.pdf. NPPG Neonatal and Paediatric Pharmacists Group Newsletter No 61 Autumn 2016. Excipients in medicines for children. http://nppg.org.uk/wp-content/uploads/2017/04/NPPG-61.pdfQuestions and Answers on Ethanol in the context of the revision of the guideline on ‘Excipients in the label and package leaflet of medicinal products for human use’ (CPMP/463/00) https://www.ema.europa.eu/en/documents/scientific-guideline/questions-answers-ethanol-context-revision-guideline-excipients-label-package-leaflet-medicinal_en.pdfEMA. Guideline on pharmaceutical development of medicines for paediatric use.https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-pharmaceutical-development-medicines-paediatric-use_en.pdf

Physical care of people suffering from schizopphrenia on risperidone long acting injectable depot

2011 ◽  
Vol 26 (S2) ◽  
pp. 1460-1460
Author(s):  
H. Najim ◽  
R. Rafiq ◽  
N. Islam
Keyword(s):  
Physical Examination ◽  
Liver Function Tests ◽  
Health Needs ◽  
List Type ◽  
Unhealthy Food ◽  
Co Morbidity ◽  
Long Acting ◽  
Physical Care

BackgroundPeople with severe mental illness neglect their physical health needs. They smoke a lot, they drink a lot and they don’t do exercise. They eat unhealthy food and put on weight. Unfortunately, the antipsychotic medication don’t help and some of the drugs are associated with side effects which make these problems worse.MethodsMedical notes of patients who has been on risperidone long term injectable depot for a year, from the first of January till the 30th 2008 were reviewed and information were input on the form.Results65 notes were reviewed. 70% males. 70% between 18-50 years. The following was done baseline:50% had physical examination.25% had pulse, blood pressure and ECG.Body weight 10%.Triglycerides 20%.Urea and electrolytes (U&E)15%.40% had their liver function tests(LFT).50% had comorbidity with other physical illness.The following were done on six monthly maintenance measures:Only 5% had maintenance ECG.LFT 10%.U&E 30%.Triglycerides 5%.DiscussionOnly 50% of patients had physical examination. Only quarter of patients had their BP, pulse and ECG done as a baseline. There was no regular physical follow up and investigation and the investigation which were done sporadically. Physical co-morbidity was 50% of the sample while physical examination and investigations were done in less than half of the sample.ConclusionsProper physical assessment and regular follow up should be adopted.Promotion of healthy living and eating, exercise and monitoring weight should be advised.

scholarly journals C-type natriuretic peptide in reproduction, pregnancy and fetal development

2004 ◽  
Vol 180 (1) ◽  
pp. 17-22 ◽  
Author(s):  
T Walther ◽  
H Stepan
Keyword(s):  
Natriuretic Peptide ◽  
Fetal Development ◽  
De Novo ◽  
Biological Effects ◽  
Endocrine Function ◽  
Comprehensive Overview ◽  
Specific Expression ◽  
Embryonic And Fetal Development ◽  
Organ Specific ◽  
Reproductive Processes

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that consists of three structurally related peptides with a 17-amino acid ring linked by a disulfide bond. In contrast to atrial and brain natriuretic peptides that are mainly cardiovascular hormones, CNP acts predominantly in an autocrine/paracrine fashion, is commonly considered to be an endothelial hormone with antimitogenic properties, and is characterized as a regulator of endochondral ossification. Its biological effects are mediated by an intracellular cGMP accumulation via specific membrane-bound guanylyl cyclase B (GC-B) activation. There is growing evidence that this peptide is also involved in various reproductive processes as well as in embryonic and fetal development. In rodents, CNP and its receptor are highly expressed in the uterus and ovaries with specific regulation during the estrous cycle. During pregnancy, CNP mRNA is detectable in mice embryos and shows an organ-specific expression in maternal reproductive tIssues with the highest concentration in the placenta. This could indicate a defined biological function of the CNP/GC-B/cGMP axis in gestation e.g. antagonizing vasoconstrictive peptides like angiotensin II. In humans, besides a postulated fetal de novo synthesis of CNP, both the peptide and its receptor are expressed in the placenta and myometrium with opposite regulation of CNP in pregnancies complicated by pre-eclampsia or intrauterine growth retardation. Since the maternal plasma levels do not reflect these alterations, one can conclude that this part of the natriuretic peptide system acts locally suggesting that CNP-stimulated cGMP release exhibits organ-specific effects. Importantly, CNP has also become a peptide with a distinct role in male reproductive processes, since endocrine function of the testis and the regulation of penile erection are regulated by the CNP/GC-B axis. This review gives a comprehensive overview of the multiple functions of CNP in reproduction and pregnancy as well as in embryonic and fetal development.

scholarly journals The clinical complexity of cases of schizophrenia in a community mental health team: a 3 year comparison

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S340-S340
Author(s):  
Shay-Anne Pantall ◽  
Laxsan Karunanithy ◽  
Hayley Boden ◽  
Lisa Brownell
Keyword(s):  
Mental Health ◽  
Primary Care ◽  
Community Mental Health ◽  
List Type ◽  
Community Mental Health Team ◽  
Service Usage ◽  
Care Programme ◽  
Mental Health Team ◽  
Health Team ◽  
Long Acting

AimsTo describe the changes in complexity and management of individuals with schizophrenia in a community mental health team (CMHT) over a three year period.BackgroundIt is often believed that individuals receiving care from CMHTs are those with low levels of complexity and risk, and are relatively stable, with more complex individuals being managed by assertive outreach or other specialist teams. Here, we describe changes in the complexity, comorbidity, service-usage and management, of patients with a diagnosis of schizophrenia in a CMHT between 2016 and 2019.MethodData were collected from an electronic patient record system (RiO) for all individuals with schizophrenia in a CMHT in Birmingham (n = 84 in 2016, n = 71 in 2019), examining demographic variables, comorbidity, use of mental health services and current management.ResultKey findings included: - •63% were managed through care programme approach (CPA) in 2016, compared to only 31% in 2019.•21% had required home treatment or inpatient care in the preceding 12 months in 2016; this had improved to 8.5% in 2019.•Significant levels of psychiatric comorbidity, including addictions with almost half of patients (46.5%) having a known history of substance use in 2019, compared to only 15.5% noted in 2016.•Pharmacological management has remained broadly similar; in 2016 21% patients were taking a combination of 2 antipsychotics compared to only 10% in 2019 and 25% were taking clozapine in 2016 (21% in 2019). 39% were prescribed a long acting antipsychotic injection in 2016, compared to 32% in 2019.•In 2016, medication was being prescribed in the majority of cases within secondary care (55%) patients and in primary care in only 21%. GPs have now taken on greater prescribing responsibility in 2019, prescribing in 44% of cases, with 47% being prescribed by the CMHT.ConclusionThe acuity and management of individuals with a diagnosis of schizophrenia under the care of a CMHT has changed over a 3 year period. It is positive to note the reduced use of crisis services and lower rates of polypharmacy. There is a reduction in the proportion of patients receiving management through CPA, and a move towards more medication being prescribed in primary care. The reasons for this change are however unclear and may reflect change in available resources, given that more than half of this group receive clozapine or long acting injections, and have high levels of comorbidity.

scholarly journals Advanced acromegaly: successful disease control for more than 16 years using octreotide LA

2020 ◽  
Vol 2020 ◽  
Author(s):  
Omayma Elshafie ◽  
Nicholas Woodhouse
Keyword(s):  
Clinical Symptoms ◽  
Tumour Size ◽  
Uncontrolled Hypertension ◽  
Therapeutic Trial ◽  
List Type ◽  
Residual Tumour ◽  
History Of ◽  
Successful Control ◽  
Long Acting

Summary A 79-year-old male presented with a 10-year history of intermittent headache, sweating, persistent hand numbness and uncontrolled hypertension. He was receiving Nifedipine and Hydrochorothizide. On examination (O/E), his BP was 180/100 he was acromegalic. His growth hormone (GH) was 10 mIU/L (0.0–0.1) and his insulin-like growth factor (IGF-1): 952 µg/L (76–160). An MRI of the pituitary revealed a 3 × 2 cm pituitary macroadenoma. Surgery was refused and the family agreed for a therapeutic trial of octreotide. His GH levels fell immediately. Two weeks later he was switched to long-acting monthly octreotide in September 2003. During his 16-year follow-up, he has remained well and asymptomatic off medications for hypertension. His BP and IGF-1 levels were also normal until octreotide Long acting (LA) octrotide was stopped for 3 months at age 96. During this period the IGF-1 level returned to pretreatment levels 500 ng/L (50–141), GH 24 mIU/L (0.0–0.1), and a small residual tumour 0.5–0.8 cm was seen on the MRI. Octreotide LA was restarted and the IGF-1 and GH levels returned to normal. He continues the same treatment to date age 97 without side effects. We conclude that the successful control of IGF-1, GH levels, hypertension, tumour size and clinical symptoms for more than 16 years occurred using octreotide LA in an elderly advanced acromegalic patient. To the best of our knowledge, this is the first report of the successful use of octreotide LA for more than 16 years. Learning points: The value of a therapeutic trial of octreotide to identify responders. Control of GH and IGF-1 secretion using octreotide LA. The report of the successful use of octreotide for more than 16 years irrespective of age.

Using Benthic Assessment Techniques To Determine Combined Sewer Overflow and Stormwater Impacts in the Aquatic Ecosystem

2000 ◽  
Vol 35 (3) ◽  
pp. 365-398 ◽  
Author(s):  
Q. Rochfort ◽  
L. Grapentine ◽  
J. Marsalek ◽  
B. Brownlee ◽  
T. Reynoldson ◽  
...  
Keyword(s):  
Biological Effects ◽  
Sediment Toxicity ◽  
Benthic Communities ◽  
Toxicity Testing ◽  
Benthic Invertebrate ◽  
Complete Characterization ◽  
Sediment Chemistry ◽  
Combined Sewer Overflows ◽  
Sources Of Pollution ◽  
Combined Sewer

Abstract Urban wet-weather sources of pollution such as Stormwater and combined sewer overflows (CSOs) can contribute significantly to the contamination of receiving waters, particularly in sediment depositional areas near outfalls. Analyses of sediment chemistry alone are not sufficient to fully assess the effects of these discharges. Toxicity testing and evaluations of benthic invertebrate communities, in conjunction with chemical analyses, provide a more complete characterization. This study assessed relationships among three separate aspects of the benthic environment:sediment chemistry (metals, PAHs and nutrients) and particle size, sediment toxicity (ten endpoints with four benthic taxa), and benthic invertebrate community structure. In this initial survey, ten sites in five different study areas, representing a range of receiving water environments exposed to Stormwater and CSO discharges, were sampled in October 1998. Results of analyses indicated that while contaminant (metals and PAHs) concentrations were relatively high in sediments, biological effects were not evident Toxicity of sediments was low and altered benthic communities were not detected. Neither toxicity endpoints nor benthic community descriptors were related to sediment contaminant levels. To improve the power of these assessments, future investigations of Stormwater and CSO discharge impacts should use “upstream/downstream” sampling designs and study sites with minimal variability of habitat conditions.

Improvement in patient symptoms and functioning during long-term treatment with olanzapine long-acting injection (OLAI)

2011 ◽  
Vol 26 (S2) ◽  
pp. 1472-1472
Author(s):  
J. Peuskens ◽  
V. Porsdal ◽  
J. Pecenak ◽  
P. Handest ◽  
Y. D’yachkova ◽  
...  
Keyword(s):  
Psychiatric Symptoms ◽  
Term Treatment ◽  
Stepwise Logistic Regression ◽  
List Type ◽  
Factors Associated ◽  
Lower Baseline ◽  
Long Term Treatment ◽  
Long Acting ◽  
Image Position ◽  
Baseline Category

Introduction, objectives and aimsTo evaluate the outcome of patients with schizophrenia during maintenance treatment with OLAI.MethodsData from three studies with OLAI were pooled and patients classified according to a cluster analysis [Lipkovich, Psychiatry Res, 2009] into five categories according severity of psychiatric symptoms (sx) and functional impairment (imp):A(minimal sx/mild imp),B(minimal sx/moderate imp),C(moderate sx/mild to moderate imp),D(moderate sx/severe imp),E(moderate to severe sx/severe imp).Improvement was defined as a change from B or C to A, or from D or E to A, B or C. Changes between the categories in the 6 months were analyzed. Stepwise logistic regression modeling was done to determine factors associated with improvement.Results1182 patients were classified. Patients who remained in the studies at 6 months had lower baseline CGI-S (3.04 vs 3.28, p < 0.001), lower PANSS (61.38 vs 64.05, p = 0.012) and higher QLS (1.76 vs 1.39, p = 0.001). (Table 1) As patients in category A couldn’t improve and in category D&E couldn’t worsen, 261(39%) patients from categories B, C, D and E improved and only 55(10%) from categories A, B and C got worse during 6 months. Baseline factors associated with improvement were: baseline category (p < 0.001), CGI-S score (p = 0.022), and PANSS positive (p = 0.003)ConclusionsMajority of patients with schizophrenia who stay on 6 months treatment with OLAI improve or maintain their symptoms and functioning level. The strongest factor associated with a higher chance of improvement was poor baseline category.

69. Biological effects of a new long-acting piogestational steroid: Org 2793

1975 ◽  
Vol 6 (11-12) ◽  
pp. xxxii ◽  
Author(s):  
J. De Visser ◽  
J. Van Der Vies ◽  
G.H. Deckers ◽  
A. Coert
Keyword(s):  
Biological Effects ◽  
Long Acting
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