Review of cetirizine hydrochloride for the treatment of allergic disorders

Cetirizine hydrochloride is an orally-active and selective histamine (H(1))-receptor antagonist. It is a second-generation antihistamine and a human metabolite of hydroxyzine. Therefore, its principal effects are mediated via selective inhibition of peripheral H(1) receptors. The antihistaminic activity of cetirizine has been documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth has been seen more commonly with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for receptors other than H(1) receptors. Auto-radiographical studies with radiolabelled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H(1) receptors. Impairment of CNS function is comparable to other low-sedating antihistamines at the recommended dose of 10 mg/day for adults. It has anti-inflammatory properties that may play a role in asthma management. It does not interact with concomitantly administered medications, it has no cardiac adverse effects, and it does not appear to be associated with teratogenicity. Cetirizine is predominantly eliminated by the kidneys with a mean elimination half-life is 8.3 h. It is rapidly absorbed, and significant clinical inhibition of a wheal and flare response occurs in infants, children and adults within 20 min of a single oral dose and persists for 24 h. No tolerance to the wheal and flare response occurs even after 1 month of daily treatment. The clinical efficacy of cetirizine for allergic respiratory diseases has been established in numerous trials. There is evidence that cetirizine improves symptoms of urticaria. Concomitant use of cetirizine also decreases the duration and amount of topical anti-inflammatory preparations needed for the treatment of atopic dermatitis. Interestingly, several clinical studies suggest that cetirizine may be useful in the treatment and prevention of mild asthma.     

Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone

The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cells. To this end, we examined the expression of two endogenous cell cycle markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar distribution in the adult mouse subgranular zone (SGZ). Quantitative analysis within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU > pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58% decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU-IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature mitosis in chronic morphine-treated mice. These results suggest that morphine-treated mice have a shorter Gap2/mitosis (G(2)/M) phase when compared to sham-treated mice. These findings demonstrate the power of using a combination of exogenous and endogenous cell cycle markers and nuclear morphology to track proliferating cells through different phases of the cell cycle and to reveal the regulation of cell cycle phase by chronic morphine.     

Partial albinism, immunodeficiency, hypergammaglobulinemia and Dandy-Walker cyst--a Griscelli syndrome variant

A 6-year-old girl presented with recurrent infections, seizures, regression of milestones, silvery hair and organomegaly. A diagnosis of Griscelli syndrome with unusual features of a Dandy Walker cyst and hypergammaglobulinemia, not previously described in literature, was made. The child was treated with supportive measures.     

Rib defects in patterns of multiple malformations: a retrospective review and phenotypic analysis of 47 cases

Rib anomalies may occur in isolation, as well as in association with abnormalities of vertebral segmentation and multi-system malformations. Specific entities include the VACTERL and MURCS associations, spondylocostal dysostosis, and spondylothoracic dysostosis. The relative significance of rib anomalies in other lesser known syndromes and associations remains unclear. To document the diagnoses and related defects in patients with rib anomalies as part of broader pattern of anomalies, we retrospectively identified 47 cases from a hospital population, and evaluated specific costal findings and associated birth defects. In our study, fusion was the most common pattern of rib anomaly (72%), followed by bifid (28%) and hypoplastic ribs (26%). Unrecognized patterns of multiple congenital anomalies (MCA) and VACTERL association were the commonest specific diagnoses with a frequency of 30 and 28%, respectively. An associated vertebral defect was found in 72% of the patients. Of those with no vertebral anomaly, the combinations of "rib and cardiac defects alone" and "rib and renal defects alone" were seen in one-third of the patients (4/13). Both the occurrence and type of rib anomaly were helpful in defining certain syndromes and enhanced the likelihood of identifying related malformations.     

Validation of verbal autopsy to determine the cause of 137 neonatal deaths in Karachi,Pakistan

Verbal autopsy (VA) aims to estimate a community's mortality experience in the absence of contact with formal registration or health care systems. Application of VA to neonatal deaths is problematic as the agonal phase of a neonatal death tends to be indistinct. This is the first attempt to validate the technique exclusively on newborns who died. Seriously ill neonates (n = 137) were enrolled from the Civil Hospital, Karachi, Pakistan, between 31 October 1993 and 31 July 1994. All died as newborns, and caregivers were interviewed at home 3-230 days later. Surveillance physicians completed case questionnaires in the hospital, and investigator physicians assigned the main and associated causes of death using clinical criteria. Field questionnaires including a verbatim open-ended history, and syndrome modules were completed by a field worker, and investigator physicians again assigned the main and associated causes of death based on three diagnostic methods: verbatim alone, modules alone and verbatim and modules combined. We assessed the validity of VA by comparing field against hospital diagnoses by diagnostic (verbatim vs. modules vs. both) and analytic method (main vs. any diagnosis). VA identified at least one diagnosis accurately in 71% of the newborns. VA underdiagnosed low birthweight and prematurity in the field. Verbatim and modules diagnostic method comparing any field against main hospital diagnoses revealed high sensitivities for too early/too small syndrome (90%) and neonatal tetanus (84%). VA correctly identified some important causes of neonatal death in the field. Assigning multiple diagnoses using both open- and closed-ended questions increases the likelihood of correct ascertainment.     

2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) induces oxidative stress in the epididymis and epididymal sperm of adult rats

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is one of the most potent environmental contaminants, which has been shown to induce oxidative stress in testis and epididymal sperm of rats. However, the nature and mechanism of action of TCDD on the epididymis is not clear. The aim of the present study was to investigate whether induction of oxidative stress in epididymal sperm was direct effect of TCDD on epididymis. In the present studies, TCDD (0.1, 1.0 and 10 micro g/kg body weight per day) was administered orally to rats for 4 days. Twenty-four hours after the last treatment the animals were killed using anesthetic ether. Both epididymides were dissected out and epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F-12 medium at 35 degrees C. The epididymal sperm and caput, corpus and cauda epididymides were homogenized and used for biochemical studies. Epididymal sperm counts did not decrease in the rats treated with TCDD. Administration of TCDD increased the production of reactive oxygen species such as hydrogen peroxide while the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were found to be decreased in the epididymal sperm as well as in cauda epididymides. Lipid peroxidation also increased in the epididymal sperm and in the various regions of the epididymides after exposure to TCDD. The results indicated that TCDD induces oxidative stress in the epididymis and epididymal sperm by decreasing the antioxidant enzymes through induction of reactive oxygen species. Thus, the adverse effects of TCDD on the epididymal sperm were due to direct effect of TCDD on epididymis.     

The floppy infant: contribution of genetic and metabolic disorders

The floppy infant syndrome is a well-recognized entity for pediatricians and neonatologists. The condition refers to an infant with generalized hypotonia presenting at birth or in early life. The diagnostic work up in many instances is often complex, and requires multidisciplinary assessment. Advances in genetics and neurosciences have lead to recognition of newer diagnostic entities (several congenital myopathies), and rapid molecular diagnosis is now possible for several conditions such as spinal muscular atrophy (SMA), congenital muscular dystrophies (CMD), several forms of congenital myopathies and congenital myotonic dystrophy. The focus of the present review is to describe the advances in our understanding in the genetic, metabolic basis of neurological disorders, as well as the investigative work up of the floppy infant. An algorithm for the systematic evaluation of infants with hypotonia is suggested for the practicing pediatrician/neonatologist.     

Preoperative diagnosis of allergic fungal sinusitis

OBJECTIVES/HYPOTHESIS: Although the diagnosis of allergic fungal sinusitis is mainly based on characteristic histopathological findings, certain preoperative diagnostic criteria have been proposed. However, their usefulness in differentiating allergic fungal sinusitis from other sinus diseases is unknown. The objective of the study was to identify accurate preoperative diagnostic parameters for allergic fungal sinusitis. STUDY DESIGN: Prospective, comparative study. METHODS: Twenty consecutive cases of allergic fungal sinusitis were evaluated prospectively and compared with 16 cases of ethmoidal polyposis and 5 cases of invasive sinus aspergillosis, with regard to various clinical, radiological, and immunological parameters. All patients were categorized based on histopathological findings. RESULTS: Nasal polyps were seen in all 20 cases of allergic fungal sinusitis, all 16 cases of ethmoidal polyposis, and 2 of 5 cases of invasive sinus aspergillosis. Computed tomography (CT) scan hyper-attenuation was seen in all 20 cases of allergic fungal sinusitis but also in 2 (13%) cases of ethmoidal polyposis and 2 (40%) cases of invasive sinus aspergillosis. Serum levels of specific anti-Aspergillus immunoglobulin E were elevated in 14 (70%) cases of allergic fungal sinusitis, 2 (13%) cases of ethmoidal polyposis, and 3 (60%) cases of invasive sinus aspergillosis. The combination of all three (ie, nasal polyps, CT scan hyper-attenuation, and elevated titers of anti-Aspergillus immunoglobulin) was not found in any case of ethmoidal polyposis or invasive sinus aspergillosis. This triad demonstrated a sensitivity of 70% and a specificity of 100% for the preoperative diagnosis of allergic fungal sinusitis. CONCLUSIONS: Nasal polyps, CT scan, and specific immunoglobulin E titers, when considered in combination, have a high preoperative diagnostic value in allergic fungal sinusitis. However, they should not be considered in isolation because considerable overlap occurs with invasive sinus aspergillosis and ethmoidal polyposis.     

Effect of lindane on testicular antioxidant system and steroidogenic enzymes in adult rats

Aim: To find out the effect of lindane on testicular antioxidant system and testicular steroidogenesis in adult male rats. Methods: Adult male rats were orally administered with lindane at a dose of 5.0 mg/kg body weight per day for 30 days. Twenty-four hours after the last treatment the rats were killed using anesthetic ether. Testes, epididymis, seminal vesicles and ventral prostate were removed and weighed. A 10% testicular homogenate was prepared and centrifuged at 4℃. The supernatant was used for various biochemical estimations. Results: The body weight and the weights of testes, epididymis, seminal vesicles and ventral prostate were reduced in lindane-treated rats. There was a significant decline in the activities of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione reductase while an increase in hydrogen peroxide (H2O2) generation was observed. The specific activities of testicular steroidogenic enzymes 3β-hydroxysteroid dehydrogenase and 1713-hydroxysteroid dehydrogenase were decreased. The levels of DNA, RNA and protein were also decreased in lindane-treated rats. Conclusion: Lindane induces oxidative stress and decreases antioxidant enzymes in adult male rats.