Pharmacological Research Progress of Novel Antihypertensive Drugs.

Cardiovascular disease stands as the leading cause of death globally, with hypertension emerging as an independent risk factor for its development. The worldwide prevalence of hypertension hovers around 30%, encompassing a staggering 1.2 billion patients, and continues to escalate annually. Medication plays a pivotal role in managing hypertension, not only effectively regulating blood pressure (BP) but also substantially mitigating the occurrence of cardiovascular and cerebrovascular diseases. This review comprehensively outlines the categories, mechanisms, clinical applications, and drawbacks of conventional antihypertensive drugs. It delves into the five primary pharmacological classifications, namely ß-receptor blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and diuretics. The emphasis is placed on elucidating the mechanisms, advantages, and research progress of novel antihypertensive drugs targeting emerging areas. These include mineralocorticoid receptor antagonists (MRAs), atrial natriuretic peptides (ANPs), neutral endopeptidase inhibitors (NEPIs), sodium-dependent glucose transporter 2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), endothelin receptor antagonists (ERAs), soluble guanylate cyclase (sGC) agonists, brain aminopeptidase A inhibitors (APAIs), and small interfering ribonucleic acids (siRNAs) targeting hepatic angiotensinogen. Compared to conventional antihypertensive drugs, these novel alternatives exhibit favorable antihypertensive effects with minimal adverse reactions. This review serves as a valuable reference for future research and the clinical application of antihypertensive drugs.

[The ultrastructural features of sputum deposition and its value in the diagnosis of pulmonary alveolar proteinosis].

OBJECTIVE: To investigate the ultrastructural features of sputum deposition (SD) and its value in the diagnosis of pulmonary alveolar proteinosis (PAP). METHODS: Seven patients with PAP diagnosed by lung biopsy and cytology were enrolled in this study. The patients consisted of 5 men and 2 women, whose median age was 48 years (range 36 to 73). SD and bronchoalveolar lavage fluid (BALF) sediment were made into ultrathin sections and observed under transmission electron microscope (TEM), respectively. Seven cases of control group composed of 4 men and 3 women whose median age was 49 years (range 39 to 68) including 3 cases of bacterial pneumonia, two cases of COPD and 2 cases of exudative pulmonary tuberculosis. Each SD was made into ultrathin section, and compared with the experimental group. RESULTS: In PAP group, Periodic acid-schiff (PAS) staining was performed on 7 sputum smears and none of them was tested positive for any components with diagnostic interest. Four cases from the 7 paraffin-embed sections of BALF sediment by microscopic examination suggested PAP. Under TEM, BALF sediment showed that many lamellar bodies existed in and outside alveolar epithelial cells, and 5 specimens were consistent with PAP diagnosis. Compared with BALF sediment, SD had apparent degeneration with more myelin phagosomes in the cytoplasm of macrophages, more lamellar bodies in alveolar epithelial cells, and lots of lamellar bodies in the shape of concentric circle in the extracellular spaces. Four from the 7 SD samples were consistent with the diagnosis of PAP. No significant difference was found between SD and BALF in the diagnosis of PAP by electronic examination (P > 0.05). In the 7 cases of control group no drifting osmiophilic lamellar bodies in extracellular space were detected. CONCLUSIONS: The osmiophilic lamellar bodies with diagnostic value were found in SD and BALF of patients with PAP. TEM of SD in combination with clinical manifestations and radiologic findings can make a definitive diagnosis of PAP, especially for those patients who have contraindications to lung biopsy and lung lavage.

[The clinical diagnosis and analysis of pulmonary mucosa associated lymphoid tissue lymphoma].

OBJECTIVE: To improve the diagnosis of pulmonary mucosa associated lymphoid tissue (PMALT) lymphoma. METHOD: The clinical and radiographic data of 13 cases of pathology confirmed PMALT lymphoma admitted from June 1998 to June 2006 were respectively analyzed. RESULTS: There were 9 males and 4 females, with an average age of 55 years. The course of the disease was 1.5 - 108 months (average 14 months). Clinical features were nonspecific, with mild symptoms including cough, chest pain, breathlessness, hemoptysis, fever, and weight loss. Some cases were suspected in the routine physical examination. Chest radiography showed multiple lesions, commonly bilateral (7/13). The lesions were of varied manifestations, including masses (2/13), nodules (2/13), increased airspace consolidation with air bronchogram (9/13) and pleural fluid (4/13). Bronchial stenosis and inflammation (6/13) were present under bronchoscopy. CONCLUSIONS: PMALT is not common, and tends to affect middle aged and older males. The disease progresses slowly and the clinical features are nonspecific.

Resistant mechanisms and molecular epidemiology of imipenem-resistant Acinetobacter baumannii.

The aim of the study was to investigate the resistant mechanisms and homology of imipenem-resistant Acinetobacter baumannii (A. baumannii). A total of 46 non-duplicate imipenem­resistant A. baumannii clinical isolates were collected from three tertiary hospitals between July, 2011 and June, 2012. The minimal inhibitory concentrations (MICs) of antimicrobial agents were determined using the agar dilution method. Phenylalanine­arginine ß-naphthylamide was used to detect the presence of the efflux pump-mediated resistant mechanism. Polymerase chain reaction was employed to amplify genes associated with drug resistance, including ß­lactamase genes, efflux pump genes and outer membrane protein gene CarO. A few amplicons were randomly selected and sequenced. Multilocus sequence analysis (MLST) was employed in typing A. baumanni. A. baumannii was resistant to imipenem, simultaneously showing resistance to several other antimicrobials. In addtition, 13 A. baumannii were found to mediate drug resistance through operation of the efflux pump. Of the various drug resistance genes tested, blaOXA­51 was present in 46 isolates, blaOXA­23 gene was present in 44 isolates and blaNDM gene was found in only one strain. Other drug resistant­associated genes, including blaKPC, blaIMP, blaOXA-24, blaOXA­58, blaSHV, blaGIM and blaVIM were not detected. Mutation of adeS and outer membrane protein gene CarO were found in a few of the imipenem­resistant isolates. The MLST analysis revealed that all 46 clinical isolates were clustered into 11 genotypes and the most frequent genotype was ST208. In conclusion, ß­lactamase genes, genes involved in efflux pump and mutation of outer membrane protein encoding gene may be important in mediating imipenem resistance in A. baumannii. Of the 11 different genotypes, ST11 was shared by the majority of A. baumannii, which may be due to horizontal transfer of patients from hospitals.

Case of interstitial lung disease possibly induced by exposure to iron dust.

Interstitial lung diseases are primarily attributable to occupational or environmental exposures to dusts and irritants. We report on a case of interstitial lung disease, possibly secondary to iron exposure. Our male patient presented with cough and shortness of breath of more than 20 years' duration after his occupational exposure had ended. A chest radiograph showed patchy shadows throughout both lower fields, and computed tomography showed ground-glass-like opacification, with fibrosis in the lower lobes. A lung biopsy revealed foamy cells in the alveolar spaces, with bronchiolitis obliterans. Microelemental analysis showed an increased level of iron in the lung tissue. After treatment with N-acetyl cysteine effervescent tablets, the patient's symptoms gradually improved. This probable case of iron-induced interstitial lung disease suggests the importance of obtaining a patient's history of occupational and environmental exposures for the sake of an accurate diagnosis.