Azelastine nasal spray inhibiting sympathetic function on human nasal mucosa in patients with allergy rhinitis.

BACKGROUND: Azelastine hydrochloride (azelastine) nasal spray is a histamine receptor-1 (H1) antagonist often used in treating allergic rhinitis to relieve its symptoms. However, the effects of azelastine to influence decongestion on human nasal mucosa in patients with allergic rhinitis are not yet fully explored and merit further exploration. The effects of azelastine on the vasocontractile responses generated by smooth muscles in the vascular structures of human nasal mucosa were investigated directly in vitro. METHODS: We examined the effectiveness of azelastine on isolated human nasal mucosa by testing: 1) the effect on mucosa resting tension; 2) the effect on mucosal contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) the effect of the drugs on electrically induced mucosal contractions. RESULTS: The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of azelastine at doses of 10â€"6 M or above elicited a significant dilation response to 10â€"6 M methoxamine-induced mucosal contraction. Azelastine could inhibit electrical field stimulation-induced spike mucosal contraction. Moreover, increase in concentration of azelastine had minimal effect on basal tension of nasal mucosa. CONCLUSIONS: The technique in our study is simple and reproducible. Azelastine could inhibit both EFS and methoxamine-induced nasal mucosal contractions in vitro. This study highlights that although azelastine nasal spray is often used in treating allergic rhinitis to improve symptoms, nasal obstruction may be not relieved immediately due to the anti-sympathetic effect of azelastine.

[Prevalence of cataract among the population aged 50 years and over at different altitudes in Gansu Province].

Objective: To assess the prevalence and influence factors of cataract at different altitudes in Gansu Province. Methods: A total of 7 560 permanent residents aged 50 years and over in seven regions of Gansu Province (altitude, 900 meters to 3 500 meters) were selected as subjects, including 2 402 males and 5 158 females, with an average age of 62.04 years. The cluster random sampling method was used to conduct the survey at village or township health service centers. The investigation procedure included questionnaire survey, pre-investigation, visual acuity examination, intraocular pressure measurement, slit lamp microscopy and fundus examination. The diagnostic criterion for cataract was typical opacity of the lens or no other eye diseases that led to visual impairment but with visual acuity less than 0.7. The prevalence of cataract was calculated according to factors such as altitude, age and sex. The Chi-square test and two-element unconditional logistic regression were used for statistical analyses. Results: A total of 7 560 people were surveyed. The prevalence rate of cataract was 39.7%, and the age-standardized prevalence was 37.7%. The prevalence of cataract increased with age (χ(2)=2 107.19, P<0.01). It was 14.1% in the group of 50-59 years, 42.9% in the group of 60-69 years and 79.2% in the group of over 70 years. The prevalence of cataract also increased with altitude (χ(2)=33.66, P<0.01). It was 36.9% in the group of altitude less than 1 000 meters, 39.0% in the group of altitude between 1 000 meters and 1 999 meters, 45.9% in the group of altitude between 2 000 meters and 2 999 meters, and 51.5% in the group of altitude more than 3 000 meters. With age stratification, the prevalence of cataract at high altitude was higher than that at low altitude (χ(2)=26.74, 16.06, P<0.01). Multivariate regression analysis showed that the risk of cataract was higher in subjects at altitude of 2 000-2 999 meters than those below 1 000 meters (OR=1.42, 95%CI 1.11-1.82), and even higher in those at altitude of 3 000 meters (OR=1.76, 95%CI 1.01-3.06). Conclusions: High altitude and old age are important risk factors for cataract, and high altitude is an independent risk factor for cataract. It is necessary for local health institutions to take measures to reduce the prevalence of blindness and low vision, especially the blindness caused by cataract. (Chin J Ophthalmol, 2019, 55:589-594).

Histone deacetylase inhibitor treatment restores memory-related gene expression and learning ability in neonicotinoid-treated Apis mellifera.

Apis mellifera plays crucial roles in maintaining the balance of global ecosystems and stability of agricultural systems by helping pollination of flowering plants, including many crops. In recent years, this balance has been disrupted greatly by some pesticides, which results in great losses of honeybees worldwide. Previous studies have found that pesticide-caused memory loss might be one of the major reasons for colony loss. Histone deacetylase inhibitors (HDACis) are chemical compounds that inhibit the activity of histone deacetylases and are known to cause hyperacetylation of histone cores and influence gene expression. In our study, the HDACi sodium butyrate was applied to honeybees as a dietary supplement. The effect of sodium butyrate on the expression profiles of memory-related genes was analysed by quantitative reverse transcription PCR. The results revealed that this HDACi had up-regulation effects on most of the memory-related genes in bees, even in bees treated with imidacloprid. In addition, using the proboscis extension reflex to evaluate olfactory learning in bees, we found that this HDACi boosted the memory formation of bees after impairment owing to imidacloprid exposure. This study investigated the association between gene expression and memory formation from an epigenetic perspective. Additionally, we further demonstrate the possibility of enhancing bee learning using HDACis and provide initial data for future research.

Effects of sumatriptan nasal spray (Imigran) on human nasal mucosa.

OBJECTIVES: Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran on human nasal mucosa have rarely been well explored, to verify the effect of Imigran, which act on human nasal mucosa directly in vitro. DESIGN AND PARTICIPANTS: We examined the effectiveness of Imigran on human nasal mucosa by testing: (i) effect on human nasal mucosa resting tension; (ii) effect on contraction caused by 10-6  mol/L methoxamine as a sympathetic mimetic; and (iii) effect of the drugs on electrically induced on human nasal mucosa contractions. RESULTS: The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Imigran at doses of 10-4  mol/L elicited a significant relaxation response to 10-6  mol/L methoxamine-induced contraction. Imigran could not inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of nasal mucosa as the concentration increased. CONCLUSIONS: The study indicated that high concentrations of Imigran had a significant spasmolytic effect by antagonising α-adreoceptors and nasal obstruction could not be released in the patient combined with acute migraine and stuffy nose by concomitant α-adrenergic agonist nasal spray plus Imigran nasal spray.

Complete response after MAID treatment for advanced primary ovarian angiosarcoma: case report and literature review.

The patient presented in this case report was a 45-year-old female, with a Stage IIIA ovarian angiosarcoma combined with mature teratoma, that underwent debulking surgery and achieved complete remission for 11 months after six cycles of MAID chemotherapy (mesna, adriamycin/doxorubicin, ifosfamide, and dacarbazine). Thereafter, she had tumor recurrence with peritoneal seeding and massive pleural effusion; hence she received chemotherapy again. Although she had been undergoing a series of chemotherapies, the tumor continued to progress. Hence, she refused further chemotherapy since September 2012. Unfortunately, she passed away in January 2013 due to severe dyspnea with wide spread tumor progression. She had the longest survival period (31 months) and complete remission period than the other advanced primary ovarian angiosarcoma cases ever reported in the literature.

Risk of refracture associated with compliance and persistence with bisphosphonate therapy in Taiwan.

SUMMARY: Bisphosphonates have been used for the treatment of postmenopausal osteoporosis since the early 1990s and studies show that compliant patients experience a lower fracture rate. This cohort study showed that the compliance of Taiwanese patients was poor and the refracture risk was related to compliance with bisphosphonate therapy. INTRODUCTION: Bisphosphonates are potent inhibitors of osteoclast activity, and reduce bone turnover by inhibiting bone resorption. According to Taiwanese reimbursement guidelines, patients with osteoporosis-related fractures are eligible for bisphosphonate treatment. This study aimed to elucidate the relationship of refracture risk with compliance/persistence with bisphosphonate therapy in Taiwan. METHODS: This was a retrospective, administrative, database analysis measuring the adherence status and impact of poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the National Health Insurance Research Database (NHIRD) were used to assemble a cohort of all osteoporosis patients who initiated bisphosphonate treatment between January 1, 2004, and December 31, 2005. Patients were followed until death, end of registration in NHIRD, or end of study period (December 31, 2006), whichever occurred first. Compliance was calculated as medication possession ratio (MPR; sum of days of supply of osteoporosis medications divided by follow-up duration). RESULTS: The refracture rates for osteoporosis patients were 5.15 %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and were significantly lower for patients with >80 % compliance than with <80 % compliance (p < 0.05). Nearly 50 % patients were noncompliant (MPR < 80 %) at 3 months, and only around 30 % patients were adherent at 1 year. Refracture risk increased with MPR < 80 %, age, and co-morbidities like diabetes mellitus or dementia. Patients with concomitant statin medication had significantly lower refracture risk. CONCLUSIONS: The compliance of Taiwanese patients with osteoporosis medication is poor, and refracture risk is related to compliance with bisphosphonate therapy.

Neuroprotective and anti-inflammatory activities of atorvastatin in a rat chronic constriction injury model.

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-beta, pIkB/IkB, NFkB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.

Predicted risk of childhood allergy, asthma, and reported symptoms using measured phthalate exposure in dust and urine.

UNLABELLED: The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3-9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3-ß-D-glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subject's health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono-n-butyl phthalate, and mono-2-ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized. PRACTICAL IMPLICATIONS: For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy-related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.

A 24.2-Mb deletion of 4q12 --> q21.21 characterized by array CGH in a 131/2-year-old girl with short stature, mental retardation, developmental delay, hyperopia, exotropia, enamel defects, delayed tooth eruption and delayed puberty.

We report molecular and cytogenetic characterization of proximal deletion of chromosome 4q, del(4)(q12 --> q21.21) in a 131/2-year-old girl with short stature, mental retardation, developmental delay, hyperopia, exotropia, enamel defects, delayed tooth eruption and delayed puberty. We speculate that haploinsufficiency of the AMTN, ENAM and AMBN genes is most likely responsible for dental disorders, haploinsufficiency of the BMP2K genes is most likely responsible for ocular disorders, and haploinsufficiency of the EREG, AREG and BTC genes is most likely responsible for delayed puberty in this patient.

[One patient with severe phenol burn complicated with acute poisoning].

On April 26, 2018, a 55-year-old male patient with severe phenol burn complicated with acute poisoning was admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine. The patient quickly developed the symptoms of central nervous system including blurred consciousness and restlessness, anuria, and respiratory failure. After self-rescue before admission and a series of measures in hospital including wound decontamination to reduce phenol absorption, rapid massive infusion and hemodialysis+ hemoperfusion, continuous renal replacement therapy for speeding up phenol excretion and organ function maintenance, the poisoning symptoms were effectively alleviated, and the patient was finally rescued successfully and discharged on post injury day 29. This case suggests that early hemodialysis combined with hemoperfusion and continuous renal replacement therapy are effective methods for treating severe phenol burn complicated with acute poisoning.

Schottky junction photovoltaic devices based on CdS single nanobelts.

Schottky junction photovoltaic (PV) devices were fabricated on single CdS nanobelts (NBs). Au was used as the Schottky contact, and In/Au was used as the ohmic contact to CdS NB. Typically, the Schottky junction exhibits a well-defined rectifying behavior in the dark with a rectification ratio greater than 10(3) at +/- 0.3 V; and the PV device exhibits a clear PV behavior with an open circuit photovoltage of about 0.16 V, a short circuit current of about 23.8 pA, a maximum output power of about 1.6 pW, and a fill factor of 42%. Moreover, the output power can be multiplied by connecting two or more of the Schottky junction PV devices, made on a single CdS NB, in parallel or in series. This study demonstrates that the 1D Schottky junction PV devices, which have the merits of low cost, easy fabrication and material universality, can be an important candidate for power sources in nano-optoelectronic systems.

Anticancer drugs: effect on the cloning of Raji lymphoma cells in soft agar.

The effect of 11 anticancer drugs on the ability of Raji lymphoma cells to form colonies in soft agar was determined with the use of both a 1-hour and a continuous drug exposure. Three distinct patterns of drug sensitivities were observed: a) Dactinomycin, adriamycin, bleomycin, mitomycin C, vincristine, and cis-platinum II all produced a dose-dependent reduction in colony formation following a 1-hour exposure, which was further augmented by a continuous exposure to the drugs; b) the antimetabolites (methotrexate, beta-cytosine arabinoside, and 5-fluorouracil) and pentamethylmelamine had no suppressive effects on colony formation with a 1-hour exposure, but they produced marked cytotoxicity with continuous drug exposure; and c) L-phenylalanine mustard had the same degree of colony suppression with both a 1-hour and a continuous drug exposure. Preincubation of Raji cells with an enzyme mixture (DNase + pronase + collagenase) did not alter the degree of colony suppression observed with the anticancer drugs. These results indicate that continuous drug exposure should be compared to a 1-hour drug incubation to determine in vitro drug sensitivities of fresh human tumors in the soft agar clonogenic assay, because the 1-hour drug exposure may not identify certain drugs that are potentially clinically active.

Sensitization of tumor necrosis factor alpha-resistant human melanoma by tumor-specific in vivo transfer of the gene encoding endothelial monocyte-activating polypeptide II using recombinant vaccinia virus.

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine with potent experimental antitumor activity. Its clinical use in cancer treatment is severely limited by its considerable toxicity after systemic administration, and it is currently confined to isolated limb and organ perfusion settings. In this report, we introduce a novel concept of TNF-alpha-based gene therapy using the TNF-sensitizing properties of endothelial cell monocyte-activating polypeptide II (EMAP-II). We hypothesized that transfer of the EMAP-II gene into established TNF-resistant human melanomas would render these tumors sensitive to subsequent systemic TNF-alpha treatment. To achieve tumor selective gene delivery, we constructed a recombinant vaccinia virus encoding the human EMAP-II gene (vvEMAP). In vitro transfection of human melanoma cells led to the production of EMAP-II by these cells. Supernatants of vvEMAP-transfected tumor cells mediated the induction of tissue factor in endothelial cells. We characterized the pattern of gene expression after systemic administration of a recombinant vaccinia virus encoding a reporter gene in a murine in vivo model of s.c. human melanoma. Gene expression in tumor tissue was increased 100-fold as compared with normal tissue, providing evidence for tumor-selective gene delivery. Finally, human melanomas in nude mice were sensitized in vivo by transferring the EMAP-II gene using vvEMAP. Subsequent systemic administration of TNF-alpha led to tumor regression and growth inhibition of these previously TNF-resistant tumors (P < 0.05). This approach using gene therapy to sensitize primarily unresponsive tumors toward TNF-alpha may enhance the usefulness of TNF-alpha in clinical treatment strategies by increasing the window for the therapeutic application of the cytokine, thus reducing the dose necessary for antitumor responses and subsequently reduce toxicity.

In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-alpha is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII).

Tumor necrosis factor (TNF)-alpha is a potent anticancer agent that seems to selectively target tumor-associated vasculature resulting in hemorrhagic necrosis of tumors without injury to surrounding tissues. The major limitation in the clinical use of TNF has been severe dose-limiting toxicity when administered systemically. However, when administered in isolated organ perfusion it results in regression of advanced bulky tumors. A better understanding of the mechanisms of TNF-induced antitumor effects may provide valuable information into how its clinical use in cancer treatment may be expanded. We describe here that the release of a novel tumor-derived cytokine endothelial-monocyte-activating polypeptide II (EMAPII) renders the tumor-associated vasculature sensitive to TNF. EMAPII has the unique ability to induce tissue factor production by tumor vascular endothelial cells that initiates thrombogenic cascades, which may play a role in determining tumor sensitivity to TNF. We demonstrate here that constitutive overexpression of EMAPII in a TNF-resistant human melanoma line by retroviral-mediated transfer of EMAPII cDNA renders the tumor sensitive to the effects of systemic TNF in vivo, but not in vitro. This interaction between tumors and their associated neovasculature provides an explanation for the focal effects of TNF on tumors and possibly for the variable sensitivity of tumors to bioactive agents.

Aiolos collaborates with Blimp-1 to regulate the survival of multiple myeloma cells.

The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) has crucial roles in the control of plasma cell differentiation and in maintaining survival of plasma cells. However, how Blimp-1 ensures the survival of plasma cell malignancy, multiple myeloma (MM), has remained elusive. Here we identified Aiolos, an anti-apoptotic transcription factor of MM cells, as a Blimp-1-interacting protein by mass spectrometry. ChIP coupled with DNA microarray was used to profile the global binding of Aiolos and Blimp-1 to endogenous targets in MM cells, which revealed their co-binding to a large number of genes, including apoptosis-related genes. Accordingly, Blimp-1 and Aiolos regulate similar transcriptomes in MM cells. Analysis of the binding motifs for Blimp-1 and Aiolos uncovered a partial motif that was similar across sites for both proteins. Aiolos promotes the binding of Blimp-1 to target genes and thereby enhances Blimp-1-dependent transcriptional repression. Furthermore, treatment with an anti-MM agent, lenalidomide, caused ubiquitination and proteasomal degradation of Blimp-1, leading to the de-repression of a new Blimp-1 direct target, CULLIN 4A (CUL4A), and reduced Aiolos levels. Accordingly, lenalidomide-induced cell death was partially rescued by reintroduction of Blimp-1 or knockdown of CUL4A. Thus, we demonstrated the functional impacts and underlying mechanisms of the interaction between Aiolos and Blimp-1 in maintaining MM cell survival. We also showed that interruption of Blimp-1/Aiolos regulatory pathways contributes to lenalidomide-mediated anti-MM activity.

Insulin autoimmunity as a cause of hypoglycemia.

"Autoimmune" hypoglycemia is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia, and insulin-binding antibodies in a patient who has never been exposed to exogenous insulin. The stimulus for insulin-antibody formation and the mechanism of the hypoglycemia in this condition remain unknown. Three patients with this rare syndrome had severe hypoglycemia of limited duration. Two had received a drug containing a sulfhydryl group (methimazole and penicillamine) as treatment for an autoimmune disorder (Graves' disease and rheumatoid arthritis, respectively). A third patient who underwent surgery for a suspected insulinoma was found to have pancreatic beta cell hyperplasia. Drugs containing a sulfhydryl group may have a role in the etiology of the syndrome. Additionally, our findings suggest a relationship between circulating insulin antibodies and beta cell hyperplasia.