Review of Pharmacologic Concepts

Early scientific knowledge recognized two basic types of substances: beneficial ones (such as foods and medicines), and harmful ones (those that cause sickness or death). The latter were designated as poisons. Modern science acknowledges that such a strict division is not justified. As early as the sixteenth century, Paracelsus recognized that ‘‘the right dose differentiates a poison and a remedy.’’ Many chemical substances or mixtures exert a whole spectrum of activities, ranging from beneficial to neutral to lethal. Their effect depends not only on the quantity of the substance to which an organism is exposed, but also on the species and size of the organism, its nutritional status, the method of exposure, and several related factors. Alcohol is a good example. Taken in small quantities, alcohol may be harmless and sometimes even medically recommended. However, an overdose causes intoxication and, in extreme cases, death. Similarly, vitamin A is required for the normal functioning of most higher organisms, yet an overdose of it is highly toxic. If the biological effect of a chemical is related to its dose, there must be a measurable range between concentrations that produce no effect and those that produce the maximum effect. The observation of an effect, whether beneficial or harmful, is complicated by the fact that apparently homogeneous systems are, in fact, heterogeneous. Even an inbred species will exhibit marked differences among individuals in response to chemicals. An effect produced in one individual will not necessarily be repeated in another one. Therefore, any meaningful estimation of the toxic potency of a compound will involve statistical methods of evaluation. To determine the toxicity of a compound for a biological system, an observable and well-defined end effect must be identified. Turbidity or acid production, reflecting the growth or growth inhibition of a culture, may be used as an end point in bacterial systems. In some cases, such as in the study of mutagenesis, colony count may be used. Similarly, measures of viable cells, cell protein, or colony count are useful end points in cell cultures.

2020 ◽  
Author(s):  
Andrés Herane-Vives

BACKGROUND “Short-term” samples are not the most appropriate for reflecting Chronic Cortisol Concentration (CCC). Although hair is used for reflecting the systemic cortisol level over “long-term”, its use appears clinically problematic. Local stress and non-stress related factors may release a circumscribed cortisol secretion that is accumulated in hair. Non-stressful earwax extraction methods may provide a more accurate specimen to measure CCC. OBJECTIVE Correlate cortisol levels using hair, serum and earwax samples METHODS Earwax from both ears of 37 controls were extracted using a clinical procedure commonly associated with local pain. One month later, earwax from the left ear side was extracted using the same procedure, and earwax from the right ear side was comfortably extracted, using an earwax self-sampling device. Participants also provided one centimetre of hair that represented the retrospective month of cortisol output, and one serum sample that reflected the effect of systemic stressors on cortisol levels. Earwax (ECC), Hair (HCC) and Serum (SCC) Cortisol Concentration were correlated and compared. Confounders´ effect on cortisol levels were studied. RESULTS Serum showed the largest and hair the lowest cortisol concentration (p<0.01). Left-ECC was larger than Right-ECC (p=0.03). Right-ECC was the only sample unaffected by confounders (all p>0.05). Right-ECC and HCC showed the only significant association (r=0.39; p=0.03). CONCLUSIONS The self-sampling device did not represent a local stressor for the ceruminous glands. It provided the cortisol level with the least likely to be affected by confounding factors over the previous month. ECC using the novel device may constitute another accurate, but more suitable and affordable specimen for measuring CCC.


2018 ◽  
Vol 28 (4) ◽  
pp. 503-509 ◽  
Author(s):  
Eva Dekens ◽  
Eufra Van Damme ◽  
Ramadan Jashari ◽  
Béatrice Van Hoeck ◽  
Katrien François ◽  
...  

2020 ◽  
Author(s):  
Hui Yin Tan ◽  
Piero R. Bianco

AbstractPriA is a member of the SuperFamily 2 helicase family. Its role in vivo is to reload the primosome onto stalled replication forks resulting in the restart of the previously stalled DNA replication process. SSB is known to play key roles in mediating activities at replication forks and it is known to bind to PriA. To gain mechanistic insight into the PriA-SSB interaction, a coupled spectrophotometric assay was utilized to characterize the ATPase activity of PriA in vitro in the presence of fork substrates. The results demonstrate that SSB enhances the ability of PriA to discriminate between fork substrates 140-fold. This is due to a significant increase in the catalytic efficiency of the helicase induced by DNA-bound SSB. This interaction is species-specific as bacteriophage gene 32 protein cannot substitute for the E.coli protein. SSB, while enhancing the activity of PriA on its preferred fork, both decreases the affinity of the helicase for other forks and decreases catalytic efficiency. Central to the stimulation afforded by SSB is the unique ability of PriA to bind with high affinity to the 3’-OH placed at the end of the nascent leading strand at the fork. When both the 3’-OH and SSB are present, the maximum effect is observed. This ensures that PriA will only load onto the correct fork, in the right orientation, thereby ensuring that replication restart is directed to only the template lagging strand.


2021 ◽  
Vol 25 (1) ◽  
pp. 107-112
Author(s):  
V. N. Ostapenko ◽  
I. V. Lantukh ◽  
A. P. Lantukh

Annotation. The problem of suicide and euthanasia has been particularly updated with the spread of the COVID-19 pandemic, which caused a strong explosion of suicide, because medicine was not ready for it, and the man was too weak in front of its pressure. The article considers the issue of euthanasia and suicide based on philosophical messages from the position of a doctor, which today goes beyond medicine and medical ethics and becomes one of the important aspects of society. Medicine has achieved success in the continuation of human life, but it is unable to ensure the quality of life of those who are forced to continue it. In these circumstances, the admission of suicide or euthanasia pursues the refusal of the subject to achieve an adequate quality of life; an end to suffering for those who find their lives unacceptable. The reasoning that banned suicide: no one should harm or destroy the basic virtues of human nature; deliberate suicide is an attempt to harm a person or destroy human life; no one should kill himself. The criterion may be that suicide should not take place when it is committed at the request of the subject when he devalues his own life. According to supporters of euthanasia, in the conditions of the progress of modern science, many come to the erroneous opinion that medicine can have total control over human life and death. But people have the right to determine the end of their lives while using the achievements of medicine, as well as the right to demand an extension of life with the help of the same medicine. They believe that in the era of a civilized state, the right to die with medical help should be as natural as the right to receive medical care. At the same time, the patient cannot demand death as a solution to the problem, even if all means of relieving him from suffering have been exhausted. In defense of his claims, he turns to the principle of beneficence. The task of medicine is to alleviate the suffering of the patient. But if physician-assisted suicide and active euthanasia become part of health care, theoretical and practical medicine will be deprived of advances in palliative and supportive therapies. Lack of adequate palliative care is a medical, ethical, psychological, and social problem that needs to be addressed before resorting to such radical methods as legalizing euthanasia.


Perfusion ◽  
2007 ◽  
Vol 22 (4) ◽  
pp. 267-272 ◽  
Author(s):  
D.C. Whitaker ◽  
A.J.E. Green ◽  
J. Stygall ◽  
M.J.G. Harrison ◽  
S.P. Newman

Introduction. The aim of the study was to investigate the relationship between S100b release, neuropsychological outcome and cerebral microemboli. Peri-operative assay of the astroglial cell protein S100b has been used as a marker of cerebral damage after cardiac surgery but potential assay cross-reactivity has limited its specificity. The present study uses an alternative enzyme-linked immunoabsorbant assay (ELISA) for serum S100b that has documented sensitivity and specificity data in patients undergoing coronary artery bypass grafting (CABG). Methods. Fifty-five consecutive patients undergoing routine CABG surgery received serial venous S100b sampling at five time points: i) Pre-operative, ii) At the end of cardiopulmonary bypass (CPB), iii) 6 hrs, iv) 24 hrs and v) 48 hrs post skin closure. A previously described sandwich ELISA with monoclonal anti- S100b was used. This assay has a lower limit of detection of 0.04 μ g/L and < 0.006% reactivity with S100a at a concentration of 100 μg/L S100a. Cerebral microemboli during surgery were recorded by transcranial Doppler monitor over the right middle cerebral artery. Evidence of cerebral impairment was obtained by comparing patients' performance in a neuropsychological battery of 9 tests administered 6—8 weeks post-operatively with their pre-operative scores. Results. There was a significant increase in S100b only at the end of bypass (mean 0.30 μg/L, SD ± 0.33 and range .00 to 1.57). S100b levels at the end of bypass did not correlate with neuropsychological outcome or microemboli counts. Conclusions. The low levels of S100b detected using the present assay, despite its high sensitivity and despite the routine use of cardiotomy suction, suggest that the assay may have higher specificity for cerebral S100b than previously used assays. There was no evidence that this assay is related to neuropsychological change or cerebral microemboli in cardiac surgery. Perfusion (2007) 22, 267—272.


2021 ◽  
Vol 100 (3) ◽  
pp. 174-182
Author(s):  
N.P. Kotlukova ◽  
◽  
T.S. Belysheva ◽  
T.T. Valiev ◽  
N.K. Konstantinova ◽  
...  

The aim of the study is to find the best approaches to the treatment of infantile hemangiomas (IH). Materials and methods of research: the experience of treatment of pediatric patients with IH of various localization is presented, which was carried out according to the protocol elaborated by the authors. Systemic therapy with propranolol, local therapy, laser therapy were used in the complex of treatment. The age of patients at the beginning of therapy ranged from 1 month up to 4,5 years. Results: in all cases, patients with propranolol treatment showed a quick and stable effect. Even at the time of the selection of the dose of the drug, IH patients began to involute, became paler, less tense. The thickness of the soft tissues in the IH area decreased by 65% compared to the baseline, the number of functioning vessels decreased by 86%. The maximum effect was achieved within the first 6 months from the start of therapy. Clinical case report – a 2,5-year-old child with extensive hemangioma of the right buttock. There was a complex treatment with propranolol, local therapy, laser therapy. The general course of treatment with propranolol was 2 years 8 months. The total number of laser interventions was 6 with the overall effect in the form of maximum regression of residual clinical manifestations of IH. A positive clinical and ultrasound picture was noted, indicating a pronounced involution of IH, and a gradual withdrawal of propranolol was started. Conclusion: the effectiveness of a comprehensive interdisciplinary approach to the treatment of extensive complicated IH was demonstrated with the participation of specialists of various disciplines: pediatricians, cardiologists, surgeons, specialists in functional and ultrasound diagnostics, specialists in laser therapy, endocrinologists in a severe premature baby with a large number of somatic problems. The clinical treatment algorithm developed and implemented for patients with IH makes it possible to avoid more aggressive methods of treatment of this pathology and to improve the quality of life of this category of patients. On the basis on the results obtained, indications for laser therapy with a selective pulsed laser were formulated.


2014 ◽  
Vol 9 (1-2) ◽  
pp. 102-140 ◽  
Author(s):  
Ritika Ganguly

This paper takes an ethnographic look at laboratory discourses and procedures in the scientific construction of contemporary ayurvedic research in India. It opens up for analysis an experiment in a ‘transdisciplinary’ research laboratory that seeks to understand the methodological and epistemic logic of ayurvedic pharmacology with the help of research methodologies specific to modern Science. In doing so, this paper unravels the various meanings that Science has for its different stakeholders. I examine—as participant, observer, and trainee—a ‘Sensory Analysis’ experiment conducted by scientists at a pharmacology and pharmacognosy laboratory for ayurvedic medicine in Bangalore. Postcolonial science studies have analysed the ways in which discourses of science lead to new knowledges and technologies as well as new ways of organising traditional medical knowledge. Yet the processes that reconcile traditional and modern methodologies of pharmacological and pharmacognostic research have received less attention. The experiment that I am discussing here revisits the ayurvedic doctrine of savours and qualities to standardise not only the parameters indicating the nature of a drug, but also standardise the human body itself as a tool to develop a specific ayurvedic methodology. I argue that in its association with the laboratory and the experimental method, the pursuit of ‘open-minded’dravyaguṇaresearch conceptualises new research in Ayurveda in terms of the right tools, simplifies complex knowledge, and reorganises the relationship of modern ayurvedic research with classical scientific thought.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17131-17131
Author(s):  
A. Papageorgiou ◽  
E. Stergiou ◽  
I. Boukovinas ◽  
G. Geromichalos ◽  
I. Stergiou

17131 Background: NSC-290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. Studies on modified steroidal esters of carboxylic derivatives of N,N-bis(2-chloroethyl)aniline, have shown that they exhibit reduced toxicity and increased antitumor activity and specificity. In this study we investigated the antitumor activity of compound A in combination with ADR (AHOP) in comparison with standard CHOP regimen. Methods: C57Bl mice were used for the antitumor evaluation of AHOP/CHOP. Experiments were initiated by implanting the tumor. LLC cells (purchased by NCI, Bethesda, USA) were implanted intramuscularly into the right hind leg as a suspension of 7 × 106 cells in 0.1 ml. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm3 and the oncostatic parameter T/C % according to the protocol of experimental evaluation of antitumor drugs of the NCI, USA. Treatments were given as a single dose (D) on day 1, intermitted dose (D/2 × 3) on days 1, 5, 9 or consecutive dose (D/4 × 9) on days 1 through 9. Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect (p < 0.05 by the Wilkoxon test). AHOP caused the maximum effect inhibiting the tumor growth by 67.7% and T/C values of 270%. CHOP was less effective producing 54.8% tumor inhibition and T/C values of 238%. Conclusions: It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the -NHCO group, combined with ADR, which intercalates between base-pairs, is the explanation for higher activity of AHOP vs. CHOP. This significant effect of NSC-290205 with the anthracycline adriamycin on LLC adds to NSC-290205 advantage for further clinical development. No significant financial relationships to disclose.


2018 ◽  
Vol 7 (1) ◽  
pp. 352-360
Author(s):  
Andressa Paganini ◽  
Elaine Caroline Boscatto ◽  
Adriano Slongo

O bolão 16 é uma modalidade esportiva onde o objetivo é derrubar nove pinos posicionados ao final de uma pista de madeira com uma bola maciça. Exige técnica, inteligência e concentração. Tendo em vista a escassez de estudos na literatura e a necessidade de aprofundar conhecimentos neste esporte específico, foi realizada a presente pesquisa para investigar a incidência de lesões e fatores relacionados às mesmas em atletas do sexo feminino, praticantes da modalidade na cidade de Caçador/SC. Trata-se de estudo transversal, descritivo, com análise quanti-qualitativa dos dados. Foi aplicado um questionário de formulário próprio para investigar informações pessoais, índice de massa corporal, tempo de jogo, dores e lesões articulares, hábitos relacionados à prática da modalidade e de outras atividades físicas. Participaram do estudo 11 atletas, com idades entre 18 a 56 anos e média de IMC 27,25 kg/m2. O tempo de prática variou de 10 meses a 27 anos. A maioria das participantes utiliza o braço direito para o lançamento e a perna esquerda para o apoio ao final do arremesso, demonstrando um movimento harmônico. No entanto, possuem alto índice de lesões/dores articulares, tendo a articulação mais acometida por dores a do joelho, seguida de quadril. Sobre o hábito de aquecimento e alongamento, todas as atletas afirmaram que o realizam; contudo foi verificado que a metade das atletas tem como prática de atividade física exclusiva o bolão, sendo necessário o incentivo a práticas preventivas voltadas ao esporte, além de orientação para a técnica adequada evitando desgaste físico entre outras consequências.Palavras-chave: Esportes. Traumatismos em atletas. Articulações. ABSTRACT: The ninepin it’s a sports mode where play mens and womens, with the objetive is drop the nine pin in the end of wooden track, with the solid ball. It requires technique, intelligence and concentration. Given the scarcity of studies in the literature and the need to deepen knowledge in this specific sport, the present research was carried out to investigate the incidence of injuries and related factors in female athletes, practitioners of the sport in the city of Caçador in Santa Catarina state. This is a cross-sectional, descriptive study with quantitative qualitative data analysis. A questionnaire was used to investigate personal information, body mass index, playing time, pain and joint injuries, habits related to the practice of the sport and other physical activities. Eleven athletes, aged 18 to 56 years, with a mean BMI of 60,075 pounds ft.sq, participated of this study. Regarding the training time, it ranged from 10 months to 27 years. Most athletes use the right arm for the throw and the left leg for support at the end of the pitch, demonstrating a harmonious movement. However, they have a high index of lesions/joint pain, and the joint is more affected by pain in the knee, followed by hip pain. On the warm-up and stretching habit, all athletes stated that they perform it. However, it was verified that half of the athletes have a practice of exclusive physical activity the ninepin, being necessary the incentive to preventive practices oriented to the sport, besides orientation for the appropriate technique avoiding physical wear among other consequences.Keywords: Sports. Athletic injuries. Joint.


2019 ◽  
Vol 10 (4) ◽  
pp. 40-48
Author(s):  
A. A. Sufianov ◽  
S. M. Karasev ◽  
R. R. Khafizov ◽  
R. R. Rustamov ◽  
R. A. Sufianov ◽  
...  

Introduction. Arteriovenous malformations (AVM) of the head represent the rare lesions that have a congenital, traumatic or post-infectious nature. In the last decade, endovascular methods have become the most prevalent in the treatment of AVM. Staged embolization is performed to achieve maximum effect and minimize the complications.Case report. A 30-year-old female patient is presented with complaints of enlarged vessels in the frontal and parietal regions. CT-angiography scan and cerebral angiography showed extracranial AVM of the fronto-parietal regions with afferent vascular supply from the right and left superficial temporal and ophtalmic arteries with significant expansion of the afferent arteries and the presence of varix dilatation of the draining veins. Two-stage endovascular embolization of AVM was performed. The first stage was embolization of the afferent vessels from the left superficial temporal artery system with exclusion of 60–65% AVM volume. Three months later, the second stage was performed with embolization of the afferent vessels from the right superficial temporal artery system and the exclusion of 75–80% of the residual volume of AVM. The non-adhesive composition SQUIDR12 (Emboflu, Switzerland) and glue composition PHILR25% (Microvention, USA) were used. A good aesthetic effect was achieved. Postoperative complications were not observed. There was no recurrence during the observation within a year.Summary. The staging and the use of various liquid embolization agents in the treatment of AVM of the head allow to achieve a good aesthetic outcome and prevent complications associated with facial soft tissue necrosis.


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