Morphological Changes of Parotid Gland in Experimental Hyperlipidemia

Objective. The aim of this study was to investigate the role of hyperlipidemia in the microstructure of parotid gland and its possible amelioration through statin treatment on Wistar rats. Methods. Forty Wistar rats (111.06 ± 3.36 g) were divided into 4 groups (A1, A2 controls, B1, B2 experimental). Groups A1 and A2 consumed normal cereal rodents diet during the experimental hyperlipidemic mixture. The A2 and B2 were treated with simvastatin (Zocor) 40 mg/kg/daily p.o. for 3 months. Results. Total cholesterol, triglycerides, high density lipoproteins, and low density lipoproteins were increased in groups B1 and B2 while the parotid weight was decreased. The histological findings demonstrated changes in the parotid gland morphology of the B1 and B2, such as the presence of chronic inflammation, fibrosis, lipocytes, and foci of lymphocytic infiltration. Conclusions. The influence of statin tended to predominate over the chronic inflammation while the lipocytes were decreased and remodelling of the parotid's structure occurred

Morphological Changes of Gingiva in Streptozotocin Diabetic Rats

Gingivitis and periodontitis are chronic bacterial diseases of the underlying and surrounding tooth tissues. Diabetes mellitus is responsible for tooth deprivation both by decay and periodontal disease. The streptozotocin-induced diabetes results in a diabetic status in experimental animals similar to that observed in diabetes patients. The aim of the study was to investigate the relationship between the gingival lesions and the microangiopathy changes in streptozotocin-induced diabetes mellitus. Forty male Wistar rats were divided into two groups (control and experimental). Diabetes mellitus was induced by 45 mg/kg IV streptozotocin. The histological investigation of the marginal gingival and the relevant gingival papilla showed inflammation of the lamina propria and the squamous epithelium as well as marked thickness of the arteriole in the diabetic group, but no changes were observed in the control group. The results suggested a probable application of a routine gingival histological investigation in diabetic patients in order to control the progress of disease complications. It may be concluded that histological gingival investigation can be used as a routine assay for the control of the diabetic disease and prevention of its complications

The role of the protein-binding on the mode of drug action as well the interactions with other drugs

Drug transport and disposition are influenced by a non-specific and reversible drug binding to plasma and tissues proteins. Albumin and a1 acid glycoprotein are the most important transport proteins of the blood. Albumin possesses specific sites for acidic and basic drug binding and can interact with them in the plasma since a third site is trapped only by digoxin. Diseases and stress conditions induce conformational changes either in plasma or in tissue proteins by the synthesis of endogenous substances which can strong interfere with the amount of the free pharmacological effective drug ratio. This may affect the binding of drugs in target molecules inducing significant pharmacokinetic alterations. Stress conditions are associated with FFA increase in serum playing an antagonistic role with other acidic molecules (e.g. ampicillin) to the same binding site. The bounded drug is displaced and freer ratio is available to interact with various organ receptors leading to pharmacological effect enhancement and therefore to side effects manifestation such as seizures. Furthermore conjunctive tissues diseases, ageing, prolonged bleeding, starvation or diseases affecting protein profile, characterized by reduced total plasma proteins, followed by albumin decrease and lessen binding sites lead to more free drug availability enhancing its pharmacological effect. Increased a1-acid glycoprotein the acute phase protein as by heart infraction or liver morbidities (e.g CC14 intoxication) mainly occupied from basic substances, in the case of cationic drug treatment resulted to the enhancement of them and consequently to pronounced effectiveness. In addition, renal failure reduced free fractions of many acidic drugs. It may be concluded that by narrowed therapeutic index of a medicine, and when drug/drug or drug/disease interactions are anticipated, drug monitoring seems to be necessary for its dosage adjustment

Effects of propranolol or paracetamol on lidocaine concentrations in serum and tissues

Purpose: The goal of this study was to determine the interaction of lidocaine after paracetamol or propranolol administration. Materials and Methods: Group A rats received a mixture of cold lidocaine and 14C lidocaine into the masseter muscle. Group B rats received lidocaine and paracetamol 7.5 mg/kg orally, whereas group C received lidocaine intramuscularly and propranolol 1.5 mg/kg orally. Five consecutive doses were administered. The levels of these drugs were estimated in serum and the total concentration and the percent protein binding of lidocaine in tissues (liver and mandible) were determined. The rats were killed 2 hours after the last dose. Results: The results suggest that lidocaine concentrations in serum were significantly increased after either paracetamol or propranolol administration. Additionally, the combined therapy of propranolol and lidocaine resulted in a significant decrease in the total concentration and the percent protein binding of lidocaine in tissues. Conclusions: The coadministration of lidocaine with paracetamol or propranolol interferes with the metabolic profile, resulting in pharmacokinetic interactions that may be significant for the determination of the correct dose of lidocaine in clinical applications. © 2003 American Association of Oral and Maxillofacial Surgeons

Stress can affect drug pharmacokinetics via serum/tissues protein binding and blood flow rate alterations

Binding of drugs to plasma and tissue proteins is critically involved in their pharmacokinetics and pharmacodynamics. Stress affects drugs' protein binding via alterations in plasma proteins' levels and excessive increase of free fatty acids due to cortisol-induced fat mobilisation. Free fatty acids play a crucial antagonistic role to drugs for the binding sites on albumin, the major binding plasma protein, resulting in subtherapeutic or toxic levels of many medications' pharmacological classes (oral anticoagulants, beta-lactames, fluoroquinolones, local anaesthetics). Upon stress, changes in blood flow rate and vascular function are also important parameters that can alter drug distribution and pharmacokinetics. Many cases are reported where stress-induced pharmacokinetic alterations led to serious clinical consequences. However, the stress affected drug activity do not always deteriorate the clinical outcome, due to the adaptive and defensive mechanisms of healthy organism. Sensitive population as patients with serious underlying diseases or after trauma or surgery should be given special attention. Clinicians should be alert and monitor cases where stress-induced drugs' pharmacokinetic modifications can have negative impact on the clinical outcome. © 2011 Springer-Verlag France