Pharmacotherapy of critical asthma syndrome: current and emerging therapies.

The critical asthma syndrome (CAS) encompasses the most severe, persistent, refractory asthma patients for the clinician to manage. Personalized pharmacotherapy is necessary to prevent the next acute severe asthma exacerbation, not just the control of symptoms. The 2007 National Asthma Education and Prevention Program Expert Panel 3 provides guidelines for the treatment of uncontrolled asthma. The patient's response to recommended pharmacotherapy is highly variable which risks poor asthma control leading to frequent exacerbations that can deteriorate into CAS. Controlling asthma symptoms and preventing acute exacerbations may be two separate clinical activities with their own unique demands. Clinicians must be prepared to use the entire spectrum of asthma medications available but must concurrently be aware of potential drug toxicities some of which can paradoxically worsen asthma control. Medications normally prescribed for COPD can potentially be useful in the CAS patient, particularly those with asthma-COPD overlap syndrome. Immunomodulation with drugs like omalizumab in IgE-mediated asthma syndromes is one important approach. New and emerging drugs address unique aspects of airway inflammation and biology but at a significant financial cost. The pharmacology and toxicities of the agents that may be used in the treatment of CAS to control asthma symptoms and prevent severe exacerbations are reviewed.

Comparison of two rapid colorimetric methods for determining resistance of mycobacterium tuberculosis to rifampin, isoniazid, and streptomycin in liquid medium.

The usefulness of two colorimetric methods for the determination of the susceptibility or resistance of Mycobacterium tuberculosis to rifampin, streptomycin, and isoniazid in liquid medium based on the reduction of 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was investigated. The agar proportion method was used as the reference method. Results obtained indicate that the sensitivity of the XTT reduction assay for the detection of rifampin resistance was comparable to that observed, and previously described, for the MTT assay. However, the reduction of XTT yields a water-soluble formazan that can be easily quantified without performing additional steps such as addition of lysing buffer and solubilization. Furthermore, the colorimetric assays, based on the reduction of XTT and MTT for the detection of isoniazid and streptomycin resistance in Mycobacterium tuberculosis, were standardized. The inhibition of MTT and

Prevention by L-alpha-phosphatidylcholine of antifungal activity in vitro of liposome-encapsulated imidazoles determined by using time-killing curves.

The antifungal activity of the imidazole derivatives miconazole and ketoconazole was reduced when they were entrapped in liposomal structures and significant differences were detected between small unilamellar vesicles (SUV) and multilamellar vesicles (MLV). To understand which component of liposomes interfered with the antifungal activity of miconazole and ketoconazole, we examined the influence of pure egg and soy L-alpha-phosphatidylcholine and cholesterol on activity against Candida albicans ATCC E10231 by time killing curves. Association of phospholipids-cholesterol-imidazole leads to an inhibitory effect on the antifungal activity comparable to that shown when miconazole or ketoconazole were entrapped in SUV liposomes or when miconazole and ketoconazole were incubated in the presence of L-alpha-phosphatidylcholine. The antifungal activity determined in the presence of cholesterol was comparable to that observed with the free drugs. Inhibition of the antifungal activity of miconazole and ketoconazole by phospholipids is dependent on the phospholipid concentration but is independent of the source of phospholipids (egg or soy). Cholesterol had no influence on the antifungal activity of the imidazoles, unlike the effect on other antifungal drugs, such as amphotericin B.

Inactivation of HSV-1 and HSV-2 and prevention of cell-to-cell virus spread by Santolina insularis essential oil.

The essential oil obtained in toto from Santolina insularis was investigated for its antiviral activity on herpes simplex type 1 (HSV-1) and type 2 (HSV-2) in vitro. The IC(50) values, determined by plaque reduction assays, were 0.88 and 0.7 microg/ml for HSV-1 and HSV-2, respectively, while the CC(50) determined by the MTT test on Vero cells was 112 microg/ml, indicating a CC(50)/IC(50) ratio of 127 for HSV-1 and 160 for HSV-2. Results obtained by plaque reduction assays also indicated that the antiviral activity of S. insularis was principally due to direct virucidal effects. Antiviral activity against HSV-1 and HSV-2 was not observed in a post-attachment assay, and attachment assays indicated that virus adsorption was not inhibited. Up to 80% inhibition of HSV-1 was achieved at the concentration of 40 microg/ml by yield reduction assay. Furthermore, reduction of plaque formation assays also showed that S. insularis essential oil inhibits cell-to-cell transmission of both HSV-1 and HSV-2.

Effects of in-vitro activity of miconazole and ketoconazole in phospholipid formulations.

Antifungal agents are often used in liposomal formulations in order to improve their pharmacological activity, but how vesicle inclusion can actually affect this is still not fully understood. We report here the results obtained from evaluation of the in-vitro activity against Candida albicans ATCC E10231 of miconazole and ketoconazole in various vesicular and non-vesicular preparations, obtained from egg and soya phospholipids, using time-kill curves. In most cases inclusion of miconazole or ketoconazole in liposomes led to a delayed and decreased activity of the drugs, with detectable differences among the various phospholipid concentrations and different liposomal preparations (small unilamellar vesicle, liposomes, multilamellar aggregates and broken liposomal structures). The results obtained may be helpful in the study of new preparations of antifungal agents entrapped in liposomal structures.

New thioxopyrimidines. Synthesis and evaluation for antimicrobial activity.

A convenient and simple synthesis of some new thioxopyrimidines was developed starting from 3-amino-3-(dialkylamino)propenethioamide derivatives. The prepared compounds were assayed in vitro for antimicrobial activity and found practically inactive.

Synthesis and antimicrobial activity of new 3,5-diaminoisothiazole derivatives.

The 3,5-diaminoisothiazole derivatives 23-42 were synthesized in excellent yields by oxidative cyclization of 3-amino-3-(dialkylamino)propenethioamide derivatives. These intermediates and the isothiazole derivatives were tested in vitro for their antimicrobial activity.

Synthesis and antimicrobial activity of some pyrrole derivatives. V: 5-Aryl-3-ethoxycarbonyl-2-(4-substituted piperazino)pyrrole derivatives.

The synthesis of new 5-aryl-3-ethoxycarbonyl-2-piperazinopyrrole derivatives is reported. The new compounds were tested in vitro for their antimicrobial activity. Compound 11 was the most active against the Gram-positive microorganisms.

[Treatment of urinary infections with ticarcillin and clavulanic acid (Clavucar) by the intramuscular route]. / Trattamento delle infezioni urinarie con ticarcillina ed acido clavulanico (Clavucar) per via intramuscolare.

20 patients suffering from hospital-acquired UTI received intramuscularly ticarcillin 1 g and clavulanic acid 200 mg for 8 days. At the end of antimicrobial therapy 84.2% of the pts presented sterile urine. After 2 weeks 68.4% of the pts continued to have sterile urine. No significant side effects were registered. The results demonstrate that the association of ticarcillin with clavulanic acid can be considered a useful option in hospital acquired UTI.

1-Acylaminoimidazoles synthesis and antimicrobial activity.

Several new 1-acylamino-2-alkyl-4-arylimidazoles were synthesized. The compounds were obtained by reaction of N1-acylacetamidrazones and alpha-bromoketones. The antimicrobial activity of the prepared compounds was tested.

Antimicrobial activity of some isothiosemicarbazones.

The microbiological activity of a series of isothiosemicarbazones is reported. The experimental data relating to the microbiological screening show an interesting antibacterial activity associated to a good antifungal activity.

Synthesis and antimicrobial activity of some 1-arylideneamino-2-mercaptoimidazole derivatives.

A new series of 1-arylideneamino-2-mercaptoimidazole derivatives obtained by condensation of 1-amino-2-mercaptoimidazole derivatives with variously substituted aromatic aldehydes is described. Investigation of their antimicrobial properties showed a good antibacterial activity for some of the tested compounds on some gram-positive micro-organisms.

Synthesis and antimicrobial activity of some pyrrole derivatives. IV--2-arylidenhydrazino-3-ethoxycarbonyl (or cyano) pyrrole derivatives.

A new series of pyrrole derivatives obtained by heterocyclization of N1-aryliden-3-ethoxycarbonyl (or cyano) acetamidrazones with alpha-bromoketones was described. The in vitro microbiological investigation showed that none of the 2-arylidenhydrazinopyrrole derivatives presented any noteworthy activity.

Synthesis and antimicrobial activity of some pyrrole derivatives. III--2-(4-arylpiperazino)-3-ethoxycarbonyl-5-aryl-pyrrole derivatives.

The synthesis of 3-ethoxycarbonyl-5-aryl-pyrrole derivatives with an arylpiperazine group in position 2 is described. The in vitro biological investigation showed that compound (XVIII) had considerable antibacterial activity against gram-positive microorganisms and antifungal activity against Candida rugosa, while the other compounds did not show any significative activity.

Synthesis and antimicrobial activity of some pyrrole derivatives. II: 2-(2'-acylhydrazino)-3-ethoxycarbonyl-5-aryl (or alkyl)- pyrrole derivatives.

A series of 2-(2'-acylhydrazino)-3-ethoxycarbonyl-3-aryl (or alkyl)-pyrrole derivatives was synthesized and submitted to in vitro microbiological screening. Most derivatives showed considerable antibacterial and antifungal activities.

Synthesis and biological activity of some pyrrole derivatives. I.

The synthesis of some 5-substituted 2-amino-3-cyano (and 3-carboethoxy)pyrroles is described starting from the cyano- and carboethoxyacetomidines and the alpha-halogeno ketones. The compounds tested in vitro as antimicrobial agents did not show any significative activity.

Synthesis and antifungal activities of N-arylideneaminoimidazole derivatives.

The synthesis and microbiological activities of 1-arylideneaminoimidazole derivatives are reported. Antimicrobial data show that some of the tested imidazoles exhibited an interesting activity on Candida albicans.

[Salmonellosis in Cagliari]. / Salmonellosi a Cagliari.

The therapy (generally ineffective) and the prophylactic measures of "Salmonellosis" are examined critically during a period of three years, 1974 -- 1976, when a large increase of infection was present in children (without letal cases). The extension of mass-vaccination, particularly by oral treatment with microbic pap of attenuate living (or dead) stock that represent the most significant antigenic groups (4, 9, 3, 6, 7, 8) is suggested.