Efficacy of mometasone furoate nasal spray for nasal symptoms, quality of life, rhinitis-disturbed sleep, and nasal nitric oxide in patients with perennial allergic rhinitis

Intranasal corticosteroid therapy has exhibited effectiveness for improving nasal symptoms and quality of life (QOL) scores associated with seasonal allergic rhinitis. We prospectively investigated the efficacy of mometasone furoate nasal spray (MFNS) for improving the total nasal symptom score, QOL score, and sleep quality in subjects with perennial allergic rhinitis (PAR). Nasal airway conditions were also objectively assessed by measuring nasal nitric oxide (NO). Fifty-seven patients with PAR were randomized to MFNS or placebo for a 14-day, double-blind, crossover study. The subjects recorded their symptoms on nasal symptom forms and a visual analog scale. QOL and sleep quality were surveyed in accordance with the Japanese version of the Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) and the Japanese version of the Epworth Sleepiness Scale. Nasal NO was measured during a single exhalation using a chemiluminescence analyzer. MFNS treatment achieved significant reductions versus placebo for total nasal symptoms (p < 0.001). There were significant decreases of the usual daily activity domain (p < 0.005), outdoor activities (p < 0.01), social function (p < 0.05), and the overall QOL score (p < 0.05) of JRQLQ with MFNS therapy versus placebo. A significant reduction of the sleepiness scale was also observed in the MFNS group with high sleep disturbance (p < 0.01). A significant decrease of nasal NO was found in the MFNS group (p < 0.01), especially among patients with severe nasal symptoms (p < 0.005). This prospective study indicated that MFNS therapy significantly improves nasal symptoms, QOL, sleep quality, and upper airway condition in Japanese subjects with PAR.     

A randomized, double-blind, placebo-controlled study of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis

Objective

Self-care with Ten-Cha is the most common complementary alternative medicine for allergic rhinitis in Japan, but evidence for an actual therapeutic effect is lacking. The purpose of the study was to investigate the effect of Ten-Cha (Rubus suavissimus) on house dust mite allergic rhinitis.

Methods

The study was performed in the otolaryngology departments of 5 facilities (Chiba University, Kagoshima University, Fukui University, Okayama University, and Nippon Medical School) from July to December 2009. A randomized double-blind study was performed with central enrollment and allocation. The subjects ingested 400 mg of Ten-Cha extract or placebo (3 capsules/day) daily for 4 weeks as a food intervention. The number of subjects was chosen with anticipation of an effect equivalent to that of mast cell-stabilizing drugs. A nasal allergy diary-based symptom score and a QOL score were used for evaluation.

Results

The Ten-Cha and placebo groups included 47 and 42 subjects, respectively. The improvement rates for sneeze, nasal discharge, nasal obstruction, and symptom scores were greater in the Ten-Cha group than in the placebo group throughout the intervention period, and the effect tended to increase with time in the Ten-Cha group. However, the differences between the groups were not significant. QOL was not significantly improved in either group.

Conclusion

Ingestion of Ten-Cha had an effect on allergic rhinitis, but the effect of Ten-Cha was limited and did not differ significantly from placebo. These results suggest that Ten-Cha does not exhibit an effect equivalent to mast cell-stabilizing drugs at the dose used in this study.     

Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers

We reported previously that subjects homozygous for the cytochrome P450 2A6 (CYP2A6) (*)4 have a lower risk of lung cancer. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for lung cancer could be found in subjects possessing novel CYP2A6 variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored CYP2A6(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for lung cancer were significantly lower in subjects who harbored CYP2A6(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the CYP2A6 genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), lung cancer risk was found to be less in subjects with the variant of CYP2A6 alleles [group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)]. The reduced risk for lung cancer was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and small cell carcinoma (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the CYP2A6 is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer.     

Conditional Deletion of Neuronal Cyclin-Dependent Kinase 5 in Developing Forebrain Results in Microglial Activation and Neurodegeneration

Neuronal migration disorders are often identified in patients with epilepsy refractory to medical treatment. The prolonged or repeated seizures are known to cause neuronal death; however, the mechanism underlying seizure-induced neuronal death remains to be elucidated. An essential role of cyclin-dependent kinase 5 (Cdk5) in brain development has been demonstrated in Cdk5^−/− mice, which show neuronal migration defects and perinatal lethality. Here, we show the consequences of Cdk5 deficiency in the postnatal brain by generating Cdk5 conditional knockout mice, in which Cdk5is selectively eliminated from neurons in the developing forebrain. The conditional mutant mice were viable, but exhibited complex neurological deficits including seizures, tremors, and growth retardation. The forebrain not only showed disruption of layering, but also neurodegenerative changes accompanied by neuronal loss and microglial activation. The neurodegenerative changes progressed with age and were accompanied by up-regulation of the neuronal tissue-type plasminogen activator, a serine protease known to mediate microglial activation. Thus age-dependent neurodegeneration in the Cdk5 conditional knockout mouse brain invoked a massive inflammatory reaction. These findings indicate an important role of Cdk5 in inflammation, and also provide a mouse model to examine the possible involvement of inflammation in the pathogenesis of progressive cognitive decline in patients with neuronal migration disorders.Mammalian brains have a highly organized neocortical structure that forms the basis for higher cognitive functions. The proper development of the neocortex requires a series of steps that begins with migration of neurons from their birth place and initiation of neurite outgrowth, and ultimately leads to differentiation of neurons and the formation of connections with their appropriate targets.¹ Recent studies have identified a large number of genes that are critical for these processes, and revealed that the mutations in these genes are associated with human neurological diseases.^2,3 Neuronal migration disorders have been diagnosed with increasingly higher frequency in patients with epilepsy refractory to medical treatment and mental retardation.⁴ Structural abnormalities arising from neuronal migration disorders contribute to hyperexcitability in the brain, primarily through the creation of abnormal neuronal circuitry that results in an imbalance between excitatory and inhibitory synaptic transmission.^5,6 The prolonged or repeated seizures are known to cause neuronal death, which may contribute to the progressive cognitive decline observed in some patients with epilepsy.⁷ Therefore, determining the molecular mechanism underlying these pathological processes is expected to have significant implications for the development of neuroprotective strategies in patients with neuronal migration disorders.Cyclin-dependent kinase 5 (Cdk5) plays an important role in various aspects of cortical development, including neuronal migration, neurite outgrowth, and axonal pathfinding.⁸ Cdk5 is a member of the Cdk family of serine/threonine kinases. Unlike other Cdks that are major regulators of cell-cycle progression, Cdk5 is predominantly involved in phosphorylation of target proteins in neurons. Direct evidence of the involvement of Cdk5 in neuronal migration came from analysis of Cdk5^−/− mice, which display perinatal lethality and extensive neuronal migration defects in the brain.^9,10 The perinatal lethality of Cdk5^−/− mice hampered our efforts to delineate the impact of Cdk5 deficiency on the postnatal brain. To circumvent this problem, we used the Cre-loxP recombination technique to generate a Cdk5 conditional knockout mouse (Cdk5 cKO). The Cdk5 gene was deleted in neurons of the forebrain by expression of cre recombinase, directed by the promoter of the CaMKII α gene encoding the α-subunit of the calcium/calmodulin-dependent kinase II (CaMKII). This strategy led to generation of viable mice with reduced expression of Cdk5 in the forebrain.Here we report that elimination of neuronal Cdk5 from the developing forebrain caused complex neurological deficits, growth retardation, and early mortality in mice. Cdk5 cKO mice exhibit not only layering defects in the forebrain but also neurodegenerative changes that are accompanied by aberrant activation of astroglia and microglia. Our data suggest that cross talk between neurons and microglia may contribute to neurodegeneration in the brain with neuronal migration disorder.     

Numerous transorbital wooden foreign bodies in the sphenoid sinus.

A very rare case of numerous transorbital wooden foreign bodies penetrating into the sphenoid sinus in a 47-year-old male is reported. His right eye was nonreactive to light, and the oculomotor, trochlear and abducens nerves were completely disturbed. Although a minor injury was observed on the inner side of the right eyebrow, the wound was not serious or infectious. Computed tomographic scanning of the orbit and parasinus revealed an isodense linear shadow to muscle and an irregular shadow of the lamina papyracea. However, the findings were difficult to discriminate from an optic canal fracture preoperatively. We detected foreign bodies penetrating the optic nerve rise, which were successfully removed in combination with an endoscopic transethmoidal and transorbital approach. Various and careful imaging examinations are recommended to diagnose and manage paraorbital trauma, when a penetrating wound of the face is observed.     

Anatomical variations of the torcular Herophili: macroscopic study and clinical aspects

The anatomical variations of the confluence of sinuses were examined, focusing on the continuity of the superior sagittal sinus (SSS) and the transverse sinuses (TSs). In the 142 specimens studied, there were 72 symmetric cases (50.7%) and 70 asymmetric cases (49.3%). The symmetric group (no dominant type) was categorized into 34 cases of bifurcation (23.9%) and 38 cases of confluence (26.8%). The asymmetric group was categorized into 54 cases of the right-dominant type (38.0%) and 16 cases of the left-dominant type (11.3%). The right-dominant type was further categorized into 38 partially-communicating (26.8%) and 16 non-communicating types (11.3%). The left-dominant type was categorized into 11 partially-communicating (7.7%) and 5 non-communicating types (3.5%). In summary, the SSS asymmetrically drained into one TS in about half of the cases studied. The right-dominant type was about three to four times as common as the left-dominant type. The draining pattern shown by the asymmetric group could provoke intracranial hypertension due to unilateral jugular vein obstruction. In order to avoid this risk in cases of neck dissection, jugular vein catheterization, or hypercoagulopathy, preoperative evaluations of the dural sinus variations via MR venography, three-dimensional CT, or plain X-ray of the skull are recommended.