Formulation and physiological factors influencing CNS delivery upon intranasal administration

The treatment of central nervous system (CNS) disorders is particularly challenging because of a variety of formidable barriers to effective and persistent delivery of therapeutic compounds. This review discusses the potential of intranasal drug administration as a means to bypass a major barrier, the blood-brain barrier, and allow for direct delivery of drugs into the CNS. The article emphasizes physicochemical properties of intranasal drug formulations as well as relevant anatomical and physiological factors in intranasal delivery of drugs for CNS therapy. Published examples of intranasal administration of small molecular weight drugs, peptides and proteins, and novel formulations for delivering a broad spectrum of molecules are discussed. Finally, the article provides several strategies for effectively enhancing nose-to-brain transport of drug molecules through rational formulation design and optimization.     

Nanoparticulate drug carriers for delivery of HIV/AIDS therapy to viral reservoir sites

Providing the optimum treatment of AIDS is a major challenge in the 21st Century. HIV is localised and harboured in certain inaccessible compartments of the body, such as the CNS, the cerebrospinal fluid, the lymphatic system and in the macrophages, where it cannot be reached by the majority of therapeutic agents in adequate concentrations or in which the therapeutic agents cannot reside for the necessary duration. Progression in HIV/AIDS treatment suggests that available therapy can lower the systemic viral load below the detection limit. However, on discontinuation of treatment, there is relapse of the infection from the reservoir sites and a potential for resistance development. This review discusses the aetiology and pathology of HIV, with emphasis on the viral reservoirs, current therapy of AIDS, and the opportunity for nanotechnology-based drug delivery systems to facilitate complete eradication of viral load from the reservoir sites. Literature-cited examples of drug delivery systems that are under investigation for the treatment of AIDS are discussed. The article also focuses on the future outlook and strategies for investigational drug formulations that use nanotherapeutic strategy for HIV/AIDS.     

Sudden infant death syndrome and reported maternal smoking during pregnancy

We investigated the effect of maternal smoking during pregnancy on the relative risk of sudden infant death syndrome (SIDS) by linking data from Georgia birth and death certificates from 1997 to 2000. We estimated the effect of misclassifying smokers as non-smokers and the effect of being misclassified on SIDS rates, and we calculated the fraction of cases caused by exposure. Of all SIDS cases, 21% were attributable to maternal smoking; among smokers, 61% of SIDS cases were attributable to maternal smoking. Maternal smoking during pregnancy is associated with a significantly increased risk of SIDS.     

Thyroid disorders in childhood and adolescence

Thyroid disorders are common endocrine problem encountered in the paediatric and adolescent age group. Amongst the functional thyroid disorders hypothyroidism is far more common than hyperthyroidism. Though simple goitre is common in this age group, nodular goitre and in particular solitary thyroid nodule are uncommon. Appropriate use of thyroid function test can delineate practically all thyroid disorders. Functional thyroid disorders lend themselves to effective treatment and monitoring strategies. The basic management principles remain similar to adults with thyroid dysfunction; experience in management of paediatric and adolescent thyroid disorders is particularly necessary to safeguard against long term detrimental effects of under-or overtreatment as it can have repercussion on the growth of the child. Prognosis in majority of the children tends to be good provided that timely and appropriate management is undertaken.     

Down in the mumps

A 10-week-old female infant presented with a right-sided facial swelling without any constitutional symptoms. The swelling was nontender, nonfluctuant, with no erythema or induration. On the basis of the clinical picture, magnetic resonance imaging findings and serology, a diagnosis of unilateral mumps parotitis was made. The United Kingdom is currently experiencing a mumps epidemic with a 28-fold rise in the number of cases over the last 10 years. Infants are being increasingly affected. Mumps parotitis, which was previously unreported in infants, needs to be considered as part of the differential diagnosis when a small child presents with swelling of the parotid gland.     

CONGENITAL TRACHEO-OESOPHAGEAL FISTULA IN A YOUNG ADULT

Congenital tracheo-oesophageal fistula (TEF) is rare in adults. Patients who present with repeated attacks of chest infection since birth or cough, choking and cyanosis during feeding should be investigated for TEF. It should be possible to detect all cases of tracheo-oesophageal fistulae using bronchoscopy, oesophagoscopy and CT either singly or in combination. These investigations also help in deciding on the route of exploration and the type of surgery. Disconnection of the abnormal fistulous tract brings dramatic relief of symptom and prevents further pulmonary damage.     

Evaluation of chemiluminescence, toluidine blue and histopathology for detection of high risk oral precancerous lesions: A cross-sectional study

Background

Chromogenic in situ hybridization (CISH) is fast becoming a well established technique for easy and sensitive determination of HER2 gene status in breast cancer. However, for the chromogenic method to achieve status as a safe and reliable technique, the method needs to be validated against already known and validated FISH techniques.

Methods

Here it is reported from a comparative study where HER2 gene status obtained by HER2 CISH pharmDx? Kit was compared to HER2 gene status obtained by the FDA approved HER2 FISH pharmDx? Kit and the PathVysion HER-2 DNA probe Kit. The study included 365 formalin fixed and paraffin-embedded invasive breast cancer tissue specimens collected consecutively at a US reference laboratory.

Results

The data obtained revealed an overall HER2 status concordance of approximately 98% for comparisons of HER2 CISH pharmDx? Kit to both HER2 FISH pharmDx? Kit and PathVysion HER-2 DNA Probe Kit.

Conclusions

The concordance between results obtained using the recently FDA approved HER2 CISH pharmDx? Kit with previously FDA approved FISH techniques for HER2 gene status determination indicate that the HER2 CISH pharmDx? Kit is a reliable chromogenic alternative to fluorescence-based methods.