Nitric oxide modulates cardiac and mast cell anaphylaxis

Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release of histamine with a long-lasting release of nitrite (NO ₂ ^– ), an oxidation product of NO.N ^G-monomethyl-l-arginine (MeArg, 300 M) increased the severity of cardiac anaphylaxis, as shown by the decrease in the coronary flow and by a prolonged duration of antigen-induced arrhythmias. Concomitantly, MeArg increased the release of histamine while decreasing the release of nitrite. Sodium nitroprusside (NaNP, 10^–5–10^–4 M) reduced the severity of cardiac anaphylaxis by increasing coronary flow and shortening the duration of antigen-induced arrhythmias. Concomitantly, NaNP decreased the release of histamine while increasing the release of nitrite. In mast cells isolated from actively sensitized guinea-pigs, the release of histamine elicited by specific antigen was increased by MeArg and decreased by NaNP.In conclusion, endogenous and exogenous NO antagonizes the effect of vasoconstrictor mediators released after antigen challenge and plays a protective role in anaphylactic reactions in vitro,     

Correlates of delayed referral for the diagnosis of dementia in an outpatient population

BACKGROUND: Early diagnosis of dementia is critical, but there is usually a time lag between onset of symptoms and referral for neuropsychological testing and dementia diagnosis. We aimed to identify factors correlated with this delayed referral. METHODS: We studied 140 patients with cognitive deterioration referred to the Memory Clinic of the Catholic University (Rome) between 1995 and 1996. Alzheimer's disease or multi-infarct dementia was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and Hachinski ischemic score. Global cognitive and neuropsychological functions were assessed with the Mini-Mental State Exam (MMSE) and the Mental Deterioration Battery. The performance on the Activities of Daily Living was used to measure physical function. The time between onset of signs of cognitive deterioration and referral for diagnosis (time to diagnosis: TTD) was estimated through a semistructured interview of the caregiver. Independent correlates of TTD were identified after adjustment for potential confounders and stratifying patients based on level of physical function. RESULTS: Of 127 eligible patients, 63% had Alzheimer's disease, 26% multi-infarct dementia, and 11% had dementia of other types. Mean age was 73.9 +/- 8.2 years, and 59% of patients were females. The mean TTD was 13.8 +/- 10.8 months and did not differ by gender, household composition, or type of dementia. For patients with normal physical function, increased age (beta = .50), female sex (beta = .51), and low MMSE score (beta = .36) were associated with longer TTD. Among patients with physical impairment, only MMSE score showed an association with TTD, but it was of opposite direction (beta = -.31). These associations were consistent by type of dementia. CONCLUSIONS: Age, gender, and degree of cognitive impairment are important correlates of the time between onset of signs/symptoms and referral for dementia diagnosis. These factors are independent of the type of dementia but are influenced by the level of physical function.     

Body mass index and mortality among hospitalized patients

BACKGROUND: Body mass index (weight in kilograms divided by the square of the height in meters [BMI]) is known to be associated with overall mortality. However, the effect of age on excess mortality from all causes associated with obesity is controversial. The aim of the present study is to determine the effect of age on the relationship between BMI and mortality. METHODS: We analyzed data from a large collaborative observational study group, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), that collected data on hospitalized patients. A total of 18,316 patients consecutively admitted to 79 clinical centers during 5 different surveys in 1998, 1991, 1993, 1995, and 1997 were enrolled in the present study. The main outcome measure was the relative hazard ratio of death for different levels of BMI. RESULTS: Mortality rate was lowest among men and women with BMIs from 25.0 through 27.4 kg/m(2) (relative risk, 0.24; 95% confidence interval, 0.15-0.38). The graphed relationship between BMI and mortality in younger patients was hyperbolic, with increased death rates at the lowest and highest BMI rankings. On the contrary, the older patients showed an increased death rate at the lowest BMIs with only a slight elevation at the highest BMIs (>35 kg/m(2)). CONCLUSIONS: Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among young and old hospitalized patients. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival. Furthermore, the finding of the high BMI associated with minimum hazard in elderly subjects supports some past findings and opposes others and, if confirmed, has important implications for geriatric clinical guidelines.     

Effects of resistance training of moderate intensity on heart rate variability,body composition,and muscle strength in healthy elderly women

Purpose

The practice of resistance training is recommended as non-pharmacological strategy during aging. In this study, we propose training composed of exercises, leg 180° press, seated row, leg curl, bench press, abduction machine, push down, adduction machine, and curl biceps. Accordingly, this study aimed to determine the effects of dynamic resistance training on autonomic response, muscle strength, and body composition of elderly women without comorbidities.

Methods

Twenty-six healthy older women (65 ± 3 years) were randomly divided into two groups. The Control Group (CG) consisted of 13 subjects not engaged in any physical exercise, while the Training Group (GT) (n = 13) performed 8 strength training exercises with 3 sets of 8 maximum repetitions. Heart rate variability, body composition, and muscle strength were assessed before and after the 12 weeks in both groups.

Results

No significant difference was found in body composition, muscle strength, and heart rate variability between CG and TG before (baseline) 12 weeks of training. Significant differences between pre- and post-training moments were found only in training group. In this sense, results demonstrated improvement (p < 0.05) in body fat mass (23.0 ± 1.2 vs. 20.0 ± 1.1 kg), fat-free mass (38.0 ± 1.5 vs. 42.0 ± 1.4 kg), strength of upper (17.8 ± 1.0 vs. 22.2 ± 1.1 kgf) and lower limbs (27.1 ± 2.4 vs. 34.1 ± 2.5 kgf), and in time and frequency domain measures of heart rate variability, highlighting the indices LF/HF (1.2 ± 0.4 vs. 0.7 ± 0.1).

Conclusions

The dynamic resistance training protocol presented in this study may be regarded as an effective approach to prevent cardiovascular morbidity and mortality in elderly women.

     

Changes in the prescribing pattern of antidepressant drugs in elderly patients: an Italian,nationwide, population-based study

Background

Despite the high use of antidepressants (ADs) among the elderly, there is limited information about the prescribing pattern of these drugs in the Italian elderly population. The aim of this study was to analyze the trend in the use of ADs in the Italian elderly patients in the years 2003-2009, and specifically, to evaluate rates and predictors of AD treatment discontinuation in depressed older patients.

Methods

The nationwide general practice Health Search Database (HSD) was used to identify AD users aged 65 years old and over from 2003 to 2009. ADs were categorized as (1) selective serotonin reuptake inhibitors (SSRIs); (2) serotonin-norepinephrine reuptake inhibitors (SNRIs); (3) tricyclic antidepressants (TCAs); (4) noradrenergic and specific serotonergic antidepressants (NaSSAs); and (5) other ADs. Incidence and prevalence of AD use per 1,000 inhabitants was calculated by drug class and single compound. We also measured rates and predictors of AD discontinuation (i.e., treatment gap?≥?60 days) during the first year of therapy.

Results

Overall, 39,557 AD users ≥65 years (17 % of the total HSD elderly population) were included in the study. SSRIs were increasingly and most frequently prescribed ADs (102.7-195.3 per 1,000 over seven years). The most common indications for AD use were depression and anxiety. Overall, 14 % of AD users continued their AD medication without treatment gaps, 27 % were intermittent AD users and 58 % discontinued their ADs during the first year of follow-up. Specific AD classes such as TCAs and ‘other ADs were found to be predictors of discontinuation. In depressed patients, the use of NaSSas, TCAs and ‘other ADs as well the concomitant use of >5 drugs (other than ADs) and living in Southern Italy were more likely to predict discontinuation.

Conclusion

ADs, especially SSRIs, are widely and increasingly prescribed in elderly Italian patients in recent years. The observed high AD discontinuation rates are likely to impact the achievement of a therapeutic endpoint in depressed patients. Patients who are at high risk of AD discontinuation such as those receiving multi-drug therapy or living in Southern Italy should be monitored more closely to improve benefits of AD treatments.     

A Cu(ii)-MOF based on a propargyl carbamate-functionalized isophthalate ligand

A copper-based metal–organic framework (MOF) was prepared using a new linker, a 5-substituted isophthalic acid bearing a propargyl carbamate group, intended to provide a terminal alkyne function protruding from the material surface to generate supported gold species for potential catalytic applications. The novel material was fully characterized by spectroscopic analyses of different kinds: FTIR, Raman, EDX, and XPS, as well as by thermal and surface area measurements. Synchrotron X-ray diffraction data analysis, in particular, revealed that this MOF, labelled [Cu(1,3-YBDC)]·xH₂O (x ∼ 2), where Y stands for the pendant alkYne and BDC for benzene dicarboxylate, contains a complex network of 5-substituted isophthalate anions bound to Cu(ii) centers, arranged in pairs within paddlewheel (or “Chinese lantern”) fragments of Cu₂(μ-COO)₄(D)₂ formulation (D being a neutral Lewis base), with a short Cu⋯Cu distance of 2.633(4) Å. Quite unexpectedly, the apical atom in the paddlewheel structure belongs to the carbamate carbonyl oxygen atom. Such extra coordination by the propargyl carbamate groups drastically reduces the MOF porosity, a feature that was also confirmed by BET measurements. However, the MOF functionality is retained at the external crystal surface where 2% of active terminal alkynes is located.

A copper-based metal–organic framework with a novel 5-substituted isophthalic linker bearing a propargyl carbamate group protruding from the material surface.     

The stress of aging

Although the evolutionary theories of aging are quite well established, our knowledge about how we age is still very limited. The abundance and heterogeneity of available mechanistic theories of aging implicitly suggest that this phenomenon is overly complex and unlikely to be explained by a single pathway. Moreover, although aging remains a unique process, it is characterized by heterogeneous manifestations, not only determining inter-individual variations, but even intra-individual diversities. Such heterogeneity renders the inner nature of the aging process of difficult evaluation in older persons due to the potential biases introduced by multiple age-related social, biological, and clinical factors (and responsible for the evidence-based issue in geriatrics). Moving from the difficulties in translating anti-aging preclinical interventions into clinical trials, an alternative approach is illustrated. We encourage moving to a holistic evaluation of aging by adopting specific and consequent modifications in the design and conduction of clinical research. Such approach is today commonly applied in the clinical setting where the complexity of older patients often requires multidimensional interventions to adequately target the geriatric syndromes. Consistently, interventions targeting the aging process may result ineffective if too focused on a single underlying causal mechanism and/or failing to capture the complexity of the phenomenon. In this context, frailty (a geriatric syndrome characterized by age-related declines occurring across multiple physiologic systems) may indeed represent a clinically relevant threshold throughout the continuum of the aging process and a promising benchmark to test multidomain interventions against age-related conditions.     

Aggressive behavior of classical Kaposi's sarcoma and coexistence with angiosarcoma

An 82-year-old Caucasian man presented with initially asymptomatic livid red plaques on the plantar surface of the feet that become confluent and evolved into invasively growing nodules accompanied by massive edema. Histology allowed a diagnosis of the classical form of Kaposi's sarcoma; the serology test result for HIV was negative, whereas the associated human herpes virus type 8 was detected by polymerase chain reaction on the skin sample. Over the subsequent 6 months, skin lesions become vegetative and partially necrotic, and extended to the hands and eyelids. Chemotherapy with vinblastine appeared to stabilize the cutaneous disease, but the patient developed a massive gastrointestinal hemorrhage secondary to dissemination to the stomach. Twelve months after the onset of the disease, vegetative and easily bleeding lesions progressively occluded the mouth of the patient: histological features were consistent with a low-grade angiosarcoma distinct from that of Kaposi's sarcoma. The patient could not chew and swallow anymore; he was put on an artificial nutrition but died shortly thereafter. This case illustrates that, even in its classical form, Kaposi's sarcoma may be a malignant, rapidly progressing tumor. LEARNING POINTS: a) The extent and rate of spread of initial skin lesions should be considered to be early signs of aggressive dissemination, even in the absence of other variables (i.e., histological pattern, human herpes virus type 8 positive mononuclear cells) associated with progression of the disease. b) An endoscopy may be useful given the high prevalence of gastrointestinal involvement. c) When classical Kaposi's sarcoma displays aggressive behavior a second, primary malignant tumor arising from the vascular tissue should be investigated. TAKE-HOME MESSAGE: Even in its classical form, Kaposi's sarcoma may be a malignant, rapidly progressing tumor with visceral involvement; also, a second malignancy may occur in nearly one patient of four. Because localized skin lesions can regress completely with radiotherapy, watchful waiting is probably inappropriate in most cases.