Time recall; future concept of chronomodulating chemotherapy for cancer.

The human metabolism is regulated by our internal clock; the circadian rhythm (24h-25h). There are several factors included in the regulatory pathway such as; genes (PER1-3), (CRY1-2), TIM hormones (cortisol, catecholamines, melatonin and insulin) drugs, enzymes, sleep disorders and diseases. Each one contributes in a different degree and in order to enhance the therapeutic result; we should include these factors into clusters instead of targeting each factor one by one. Malignances deregulate gene-protein expression/production, enzyme production, and in addition they induce fatigue, insomnia, stress and sleep disorders. All these factors finally contribute in minimizing the efficiency of chemotherapy treatment and quality of life. In addition, the circadian rhythm disruption induces tumor genesis, stress, and downregulates the defense and repair mechanisms of the human body. In the current mini review the underlying mechanism of the circadian rhythm is provided, along with the influence of sleep disturbances in cancer patient therapy. A proposal is presented to divide circadian rhythm and sleep disturbances into two major clusters with different management, however; with a common target to improve treatment efficiency and quality of life. Finally, a chrono-chemotherapy administration model is proposed in order to have less chemotherapy side effects.

Vitamin D in asthma and future perspectives.

Humans have the ability to synthesize vitamin D during the action of ultraviolet (UV) radiation upon the skin. Apart from the regulation of calcium and phosphate metabolism, another critical role for vitamin D in immunity and respiratory health has been revealed, since vitamin D receptors have also been found in other body cells. The term "vitamin D insufficiency" has been used to describe low levels of serum 25-hydroxyvitamin D that may be associated with a wide range of pulmonary diseases, including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. This review focuses on the controversial relationship between vitamin D and asthma. Also, it has been found that different gene polymorphisms of the vitamin D receptor have variable associations with asthma. Other studies investigated the vitamin D receptor signaling pathway in vitro or in experimental animal models and showed either a beneficial or a negative effect of vitamin D in asthma. Furthermore, a range of epidemiological studies has also suggested that vitamin D insufficiency is associated with low lung function. In the future, clinical trials in different asthmatic groups, such as infants, children of school age, and ethnic minorities are needed to establish the role of vitamin D supplementation to prevent and/or treat asthma.

New insights in the production of aerosol antibiotics. Evaluation of the optimal aerosol production system for ampicillin-sulbactam, meropenem, ceftazidime, cefepime and piperacillin-tazobactam.

BACKGROUND: Several aerosol antibiotics are on the market and several others are currently being evaluated. Aim of the study was to evaluate the aerosol droplet size of five different antibiotics for future evaluation as an aerosol administration. MATERIALS AND METHODS: The nebulizers Sunmist(®), Maxineb(®) and Invacare(®) were used in combination with four different "small <6 ml" residual cups and two "large <10 ml" with different loadings 2-4-6-8 ml (8 ml only for large residual cups) with five different antibiotic drugs (ampicilln-sulbactam, meropenem, ceftazidime, cefepime and piperacillin-tazobactam). The Mastersizer 2000 (Malvern) was used to evaluate the produced droplet size from each combination RESULTS: Significant effect on the droplet size produced the different antibiotic (F=96.657, p<0.001) and the residual cup design (F=68.535, p<0.001) but not the different loading amount (p=0.127) and the nebulizer (p=0.715). Interactions effects were found significant only between antibiotic and residual cup (F=16.736, p<0.001). No second order interactions were found statistically significant. CONCLUSION: Our results firstly indicate us indirectly that the chemical formulation of the drug is the main factor affecting the produced droplet size and secondly but closely the residual cup design.

Establishing the optimal nebulization system for paclitaxel, docetaxel, cisplatin, carboplatin and gemcitabine: back to drawing the residual cup.

BACKGROUND: Chemotherapy drugs have still the major disadvantage of non-specific cytotoxic effects. Although, new drugs targeting the genome of the tumor are already in the market, doublet chemotherapy regimens still remain the cornerstone of lung cancer treatment. Novel modalities of administration are under investigation such as; aerosol, intratumoral and intravascular. MATERIALS AND METHODS: In the present study five chemotherapy drugs; paclitaxel, docetaxel, gemcitabine, carboplatin and cisplatin were nebulized with three different jet nebulizers (Maxineb(®), Sunmist(®), Invacare(®)) and six different residual cups at different concentrations. The purpose of the study was to identify the "ideal" combination of nebulizer-residual cup design-drug-drug loading for a future concept of aerosol chemotherapy in lung cancer patients. The Mastersizer(®) 2000 was used to evaluate the aerosol droplet mass median aerodynamic diameter. RESULTS: The drug, nebulizer and residual cup design greatly influences the producing droplet size (p<0.005, in each case). However; the design of the residual cup is the most important factor affecting the produced droplet size (F=834.6, p<0.001). The drug loading plays a vital role in the production of the desired droplet size (F=10.42, p<0.001). The smallest droplet size was produced at 8 ml loading (1.26 µm), while it remained the same at 2, 4 and 6 mls of drug loading. CONCLUSION: The ideal nebulizer would be Maxineb(®), with a large residual cup (10 ml maximum loading capacity) and 8 mls loading and the drug with efficient pulmonary deposition would be docetaxel.

Long-term respiratory follow-up of H1N1 infection.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus infection was documented in our Hospital on 10th August 2009. METHODS AND FINDINGS: Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm the diagnosis. All patients were treated with oseltamivir from the first day of hospitalization. Upon admission 12/44 had local patchy shadowing in their chest x-ray and additionally antibiotic regimen was added to these patients as pneumonia was suspected based on clinical evidence. In total 44 patients were hospitalized 15/44 had asthma, 6/44 COPD, 5/44 leukemia. Lung function was evaluated with forced vital capacity, forced expiratory volume in 1 sec and diffused carbon monoxide upon discharge and every 3 months, until 6 months of observation was completed after discharge. The purpose of this retrospective cohort study was to evaluate whether influenza A (H1N1) had an impact on the respiratory capacity of the infected patients. CONCLUSIONS: An improvement of pulmonary function tests was observed between the first two measurements, implicating an inflammatory pathogenesis of influenza A (H1N1) to the respiratory tract. This inflammation was not associated with the severity or clinical outcome of the patients. All patients had a mild clinical course and their respiratory capacity was stable between the second and third measurement, suggesting that the duration of respiratory inflammation was two months. Early treatment with antiviral agents and vaccination represent the mainstay of management.

Inhaled insulin: too soon to be forgotten?

Inhalation is a potentially viable route of administration for numerous agents. In diabetes mellitus, the need for frequent injections to achieve ideal glycemic control remains a significant limitation for initiating and complying with insulin therapy in a large number of patients. To overcome this barrier, inhaled insulin was developed. The inhalation form of regular human insulin has been tested and administered in a large number of trials. Respiratory capacity was evaluated in patients with normal lung parenchyma in whom inhaled insulin was administered without complications. However, issues like cost, bulky device, fear for lung safety, and the small number of studies in subjects with underlying respiratory disease prevented widespread use of this new mode of delivery. In the present review, we will suggest a number of methods that could be applied in this form of administration to maximize drug absorption and fully exploit the advantages of this route of administration.

Sarcoidosis-associated pulmonary hypertension: a role for endothelin receptor antagonists?

Data on the treatment of sarcoidosis-associated pulmonary hypertension are scarce, while the variety of underlying pathophysiologic mechanisms are a major limitation in the implementation of a universal therapy. We report a 47-year-old male patient who presented with stage II sarcoidosis and associated severe pulmonary hypertension. Corticosteroid treatment resolved parenchymal lesions of the lung while vascular involvement did not respond, with the patient remaining in poor functional status. Addition of bosentan, a dual endothelin receptor antagonist, resulted in marked improvement in functional class and exercise capacity of the patient, allowing gradual tapering of steroids.