Experimental Pharmacological Research Regarding the Potential Antidepressant Activity Induced by Some Newly Synthesised Dibenzo[a,d]cycloheptene Compounds

Background. Depression is a relatively frequent encountered mental disorder in the general population, affecting both the quality of the individual life and its ability to perform the social tasks; it is generally accepted that new studies related to this pathologic condition are further necessary, in order to identify more adequate, efficient and accessible therapeutic compounds. Materials and Methods. This study was performed on a sample of 60 white male mice, NMRI strain, who were divided into 6 groups of 10 animals and treated with 4 new derivatives of dibenzo [a, d] cycloheptene, amitriptyline as a reference substance, or with distilled water for the control group. The animals were tested in respect to the forced swim test, both before and at 2 hours after administration of the mentioned substances. It was determined thus the time of immobilization. Results. The study showed the fact that only two of the four investigated compounds presented a relatively similar antidepressant effect with the reference substance. Conclusions. Minor structural changes, such as modifications of some substitutes from the basic chemical core of the reference substance can decisively influence the conservation or loss of the antidepressant properties

Metoclopramide Neurological Side Effects Screening; A Pharmacovigilence Study in Romanian Community Pharmacies

Background. Metoclopramide is a pharmacological agent frequently used in therapy against nausea and vomiting that can occur in indigestion, motion sickness, gastric ulcer, pyloric spasm and after surgery as a side effect of some anesthetics. Knowing the frequency and intensity of metoclopramide neurological side effects is essential for an efficient management of the dysfunctions it addresses. Material and method. Based on a standard questionnaire containing questions regarding metoclopramide therapy, we analyzed the answers given by 1000 patients or patient tutors in 20 open circuit pharmacies situated all over Bucharest. All subjects freely consented to participate in this study that was coordinated only by pharmacists. Results. Our study highlights the fact that in certain situations having to do with the age of patients, with the use of multiple drugs or with the tendency to self medicate, the neurological side effects of metoclopramide can reach dangerous levels. In some cases it might even be necessary to immediately interrupt metoclopramide therapy, despite its positive benefit/ risk ratio. Conclusions. Respecting the physician’s recommendations, avoiding self medication and reporting side effects as quickly as possible, are essential elements for minimizing the consequences of metoclopramide side effects

Experimental pharmacological research regarding some newly synthesized benzamides on central nervous system functions

Three newly synthesized benzamides by the Department of Pharmaceutical Chemistry of the Faculty of pharmacy from the University of Medicine and Pharmacy „Carol Davila” Bucharest were tested in order to determine whether these new molecules have similar effects on the central nervous system as those already in therapeutic use belonging to the same chemical group, such as tiapride (neuroleptic) or lidocaine (local anaesthetic). Tests were carried out on NMRI mice which were given new compounds, conventionally named I5C, I14C, and II5C in a dose of 1/20 of the lethal dose 50% (LD50), as previously determined. They received this treatment daily for 21 days. The evasive–investigating capacity of mice was determined using the platform test, and the motor activity using an Activity cage device. The results have shown that compounds I5C and II5C decrease the investigation capacity of the mice; and compound I5C inhibits motor activity, while II5C stimulates it. Thus we concluded that only compounds I5C and II5C have a neuroleptic potential that might be investigated further

Primary hyperparathyroidism can generate recurrent pancreatitis and secondary diabetes mellitus – A case report

Introduction. Acute or recurrent pancreatitis may be a complication of primary hyperparathyroidism and patients with previous episodes of pancreatitis may develop secondary diabetes mellitus. Case report. We describe the clinical case of a 52-year old Caucasian man diagnosed with chronic recurrent pancreatitis in 2007. The first episode of acute pancreatitis occurred in 2002, followed by another 4 episodes in 2004 and 2007. In 2004, papilosfincterectomy was implemented with a stent mount that was removed one month later. In 2005, the patient underwent a surgical intervention for the diagnosis of chronic lithiasis, and cholecystectomy was performed. Additional investigations on the etiology of recurrent chronic pancreatitis, initially diagnosed as idiopathic, revealed elevated values of total serum calcium, serum parathormone, and the presence of a parathyroid adenoma in the right lower pole of the thyroid. In September 2007, parathyroidectomy was performed with a favorable evolution and the remission of the acute pancreatitis episodes. The patient had not had any family history of diabetes; in 2017 he was diagnosed with diabetes. Conclusion. In cases of recurrent pancreatitis, screening for hyperparathyroidism is recommended. Metabolic evaluation is required, because the risk of developing diabetes in patients with recurrent pancreatitis is high

The role of biotransformation processes in mediating interactions between psychotropic drugs and natural products

Many patients are not aware that natural products such as fruit juices or plant infusions can cause significant interactions with several drugs, some of which can be dangerous, especially when the medical treatment is for neurological or psychiatric disorders. Among the most predisposed for interacting with drugs are citric juices, particularly grapefruit and plant infusions, especially St John`s wort (Hypericum perforatum). Understanding the mechanism and the frequency of this type of interaction helps to avoid it. The goal of this research was to identify and summarize the most relevant reports on interactions between psychotropic drugs and natural beverages, in order to raise awareness among physicians that they should invest more time in educating patients how to administer drugs properly, thus reducing the likelihood of such unwanted events. For the purpose of this study, an electronic search of PubMed database was conducted until September 2019. We concluded that natural beverage consumption along side medical treatment is a widespread practice and the main mechanism generating interactions is related to the functioning of biotransformation enzymes

Serum markers of bone fragility in type-2 diabetes mellitus

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD. The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic fractures, but do not include risk factors specific to illness such as diabetes duration, diabetes drug therapy, glycemic control, or the presence of micro-vascular complications. Multiple markers have been investigated to provide information on the risk of fractures in patients with T2DM such as: advanced glycation end products (AGEs), insulin-like growth factor-I (IGF-I), osteocalcin (OC), adiponectin, and sclerostin, but epidemiological studies did not provide homogeneous information regarding the link between these markers and bone fragility in T2DM subjects. Markers that increase the accuracy of fracture risk estimation in patients with T2DM need to be identified and employed in current medical practice

Primary hyperparathyroidism can generate recurrent pancreatitis and secondary diabetes mellitus – A case report

Introduction. Acute or recurrent pancreatitis may be a complication of primary hyperparathyroidism and patients with previous episodes of pancreatitis may develop secondary diabetes mellitus. Case report. We describe the clinical case of a 52-year old Caucasian man diagnosed with chronic recurrent pancreatitis in 2007. The first episode of acute pancreatitis occurred in 2002, followed by another 4 episodes in 2004 and 2007. In 2004, papilosfincterectomy was implemented with a stent mount that was removed one month later. In 2005, the patient underwent a surgical intervention for the diagnosis of chronic lithiasis, and cholecystectomy was performed. Additional investigations on the etiology of recurrent chronic pancreatitis, initially diagnosed as idiopathic, revealed elevated values of total serum calcium, serum parathormone, and the presence of a parathyroid adenoma in the right lower pole of the thyroid. In September 2007, parathyroidectomy was performed with a favorable evolution and the remission of the acute pancreatitis episodes. The patient had not had any family history of diabetes; in 2017 he was diagnosed with diabetes. Conclusion. In cases of recurrent pancreatitis, screening for hyperparathyroidism is recommended. Metabolic evaluation is required, because the risk of developing diabetes in patients with recurrent pancreatitis is high

Experimental pharmacological research regarding some new quinazolin-4-ones derivatives

A series of new compounds with quinazolin-4-one structure, synthesized by the Pharmaceutical Chemistry Department of the Faculty of Pharmacy of the University of Medicine and Pharmacy “Carol Davila” Bucharest, was studied. Five of them were selected, conventionally named S1, S2, S3, S4, S5, and investigated in terms of their potential influence on the central nervous system (CNS). For this purpose, the antidepressant effect was determined using the forced swimming test; the anxiolytic/ anxiogenic effect was determined using the suspended plus-shaped maze (Ugo Basile); the effect on the motor activity was determined using the Ugo Basile activity cage; and the potential analgesic effect was investigated using the hot plate test (Ugo Basile). Compounds S3 and S5 lowered the motor activity and showed an anxiolytic effect, while S1 and S2 proved to have antidepressant and analgesic effects. A good correlation between antidepressant and analgesic effects was observed, consistent with the fact that analgesic drugs, by increasing norepinephrine and serotonin levels in the pain inhibiting descendent pathways, can be used as co-analgesics in therapy

Oral pathology induced by excess or deficiency of glucocorticoids in adults

Oral manifestations are present both in Cushing\u27s syndrome and in adrenal insufficiency. Possible oro-dental pathology in patients with Cushing\u27s syndrome include jawbone loss, tooth loss, and periodontal diseases. Professional societies did not include Cushing\u27s syndrome as being part of systemic diseases associated with loss of periodontal supporting tissues. The comorbidities of Cushing\u27s syndrome such as obesity, osteoporosis, and diabetes are conditions that influence periodontal attachment apparatus. In patients with adrenal primary insufficiency, the most specific sign is the melanic pigmentation of the skin and mucosal surfaces due to increments of corticotropin and pro-opiomelanocortin peptide levels that occur as a result of decreased cortisol feedback. The oral mucosa develops black plaques that can also be present on the gums, palate, tongue, and lips. The pallor may occur in patients with adrenocortical insufficiency secondary to corticotropin deficiency. Patients with primary adrenal insufficiency need to increase their glucocorticoid doses during physical activity, intercurrent illnesses, surgery, and medical procedures. Current evidence indicates that routine, nonsurgical, or minor surgical procedures do not need supplemental glucocorticoids in diagnosed patients who are in a stable condition. However, for major oral surgery, glucocorticoid supplementation is necessary for the surgery day and for at least one postoperative day

Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice

The severity and complexity of depression can vary widely among individuals, thus making single drug therapy ineffective in some cases. Taking this fact into account and using a mouse model, we set on investigating the possibility of obtaining a synergism of action between a classical tricyclic antidepressant that inhibits noradrenalin and serotonin reuptake (doxepin), and a modern antidepressant that inhibits type-B monoamine oxidase (selegiline). We measured the antidepressant effect using the forced swimming test and the tail suspension test. We determined motor activity using the Activity Cage test. Our results have shown that the antidepressant effect intensifies significantly in the animals treated with both antidepressants simultaneously compared to those treated only with doxepin. Furthermore, we observed that selegiline decreases the sedative effect of doxepin in the Activity Cage test