Cytokine release from osteoblasts in response to ultrasound stimulation

Bone is a dynamic tissue with a well-balanced homeostasis preserved by both formation and resorption of bone. Normal turnover of bone, however, can be upset by either increased osteoclast activity or decreased osteoblast function; either mechanism alone or both may result in a net loss of bone. Both osteoclasts and osteoblasts could be stimulated by mechanical stimulation in vitro, and it is assumed that this process may occur in vivo as well. In this experiment, we investigated this hypothesis by examining the effects of ultrasound stimulation on osteoblast growth and cytokine release. With this model, we explored the mechanism of low-intensity pulsed ultrasound on osteoblasts growth and upregulation of osteoclasts formation and function by cytokine release. The results showed that specific pulsed ultrasound exposure could enhance osteoblasts population together with increase in TGFbeta1 secretion and decrease in concentration of IL-6 and TNFalpha in the culture medium. Although, animal studies and clinical trial are needed to understand the real process in the whole body, ultrasound stimulation might be a good method for prevention of bone loss due to osteoporosis.     

Acute bacterial nephritis: a clinicoradiologic correlation based on computed tomography.

PURPOSE: Acute bacterial nephritis (ABN) represents localized, nonliquefied renal infection, and the subsequent alteration of tissue densities can be readily detected by computed tomography (CT). In recent literature, a variety of renal parenchymal alterations observed on CT were reported. However, previous reports on the clinical course of ABN were inconsistent and lacked correlation with radiologic findings. In this investigation, we attempt to correlate the severity of clinical manifestations with CT findings in ABN and draw some conclusions regarding the natural history, pathophysiology, and clinical management of this disease. PATIENTS AND METHODS: From July 1988 to June 1991, 30 cases of ABN were evaluated at our institute. On the basis of postcontrast-enhanced CT findings, 28 cases were grouped into (1) Group I (7 cases), wedge-shaped lesions (focal or diffuse); (2) Group II (12 cases), focal mass-like lesions; and (3) Group III (9 cases), diffuse (multifocal) mass-like lesions. The clinical features and outcomes of the three groups were compared. The positive detecting rates and clinical usefulness of ultrasonographic (US) and urographic examinations were also studied in each group. RESULTS: An excellent correlation can be demonstrated between the clinical parameters (including underlying diseases, maximum temperature and leukocyte count, duration of fever, flank pain, leukocytosis, and pyuria; the incidence of septic shock, diabetic ketoacidosis, and acute renal failure; and outcome) and the pattern of renal parenchymal abnormalities detected on CT. The clinical features in Group I patients displayed many similarities with those in uncomplicated acute pyelonephritis (APN) reported previously, and responded to antibiotic therapy promptly. Most patients in Group II were successfully treated with antibiotics but had a protracted clinical course with a slower clinical improvement than Group I. Only one case with a Group II lesion was noted to progress to renal abscess formation and extrarenal involvement. In comparison, 33% of the patients in Group III died despite antibiotic therapy. Our data also show that US examination is sensitive in detecting Group II ABN lesions (62% positive rate), and revealed marked renal enlargement in most Group III lesions (89%). It is therefore a useful initial imaging modality in providing information vital to clinical decision making. CONCLUSION: Our experiences suggest that renal bacterial infection may show the continuum of severity from uncomplicated APN to ABN, demonstrated on postcontrast CT scan as wedge-shaped lesions to mass-like lesions, and possibly, finally to frank abscess formation. We classify ABN into three subgroups according to CT findings, and good correlation with clinical severity is demonstrated. These findings deliver valuable concepts regarding the pathophysiology and clinical management of this disease.     

Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells

ObjectivesUrothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system. Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed.Methods and MaterialsCellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential.ResultsReduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa hydrostatic pressure.ConclusionsBoth MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor.     

Mixed acid fermentation of glucose as a mechanism of emphysematous urinary tract infection

Emphysematous pyelonephritis is a severe necrotizing infection that usually occurs in patients with diabetes mellitus or obstructive uropathy. Although glucose fermentation has been considered as the main cause of gas production the actual mechanism remains controversial. Compositions of gas samples from 2 patients with emphysematous pyelonephritis recently encountered were analyzed, and showed 15% hydrogen, 4.8% carbon dioxide, 60% nitrogen, 6.7% oxygen and some unknown gases in case 1, and 3.4% hydrogen, 22% carbon dioxide, 66% nitrogen and 9.8% oxygen in case 2. These results tend to implicate mixed acid fermentation of glucose as the pathway by which emphysematous urinary tract infections develop.     

A novel application of indolicidin for gene delivery

A bovine derived antimicrobial peptide, indolicidin (IL), was studied of its new application for gene transfer. Plasmid DNA was complexed with both IL and polyethylenimine (PEI) as ternary particles. Compared to DNA/IL complexes, the DNA/IL/PEI particles demonstrated high zeta potentials, small particle sizes, and superior loading efficiencies, suggesting the incorporation of polycations can support IL for gene delivery. For in vitro experiments, these ternary particles significantly improved gene transfection efficiencies over the sole administrations of IL or PEI. This synergistic effect revealed that IL and PEI may play different roles for gene transfer. Our results suggest that IL should be a potential carrier for gene delivery. As our knowledge, our study should be the first article indicating the carrier ability of IL for gene transfer.     

Comparison of ultrasound and electromagnetic field effects on osteoblast growth

This study compares the mechanisms of ultrasound (US) on osteoblast proliferation with those of pulsed electromagnetic field (PEMF), by different signal transduction pathway inhibitors. The cells were stimulated for 15 min under US or for 2 h under PEMF exposure. Twenty-four h after the beginning of stimulation, the cells were harvested and used for mitochondrial activity test (MTT) analysis. The results showed that there are different transduction pathways for US and PEMF stimulation that lead to an upgrade of osteoblast proliferation, although their pathways all lead to an increase in cytocolic Ca2+ and activation of calmodulin. These findings offer a biochemical mechanism to support the process of ultrasound and PEMF-induced enhanced healing of bone fractures.     

High-glycolytic cancers and their interplay with the body's glucose demand and supply cycle

Many difficult-to-treat solid cancer tumours and metastases have high-glucose uptake, usually under hypoxic conditions. Hypoxic tumours suppress the immune system and are insensitive to traditional chemoradiotherapies. The only therapy usually available is surgical resection. However, with widespread metastases, surgery often becomes unviable. Surgery in itself can also result in metastasis. The need for investigating adjuvant treatments is obvious. Here we investigate whether the high-glucose uptake of hypoxic tumours could lead to such a treatment. Before any treatment can be hypothesised, it is crucial to understand how this glycolytic cancer phenotype fits in with the normal body's blood glucose cycle. The brain creates the healthy body's largest demand for blood glucose (BG) and ensures a very high level of control on in vivo supply. It is hypothesised that, through somatic evolution, high-glycolytic cancer cells opportunistically tap into this very stable energy environment. It is shown that therapies which target the glycolytic cancers' high BG needs cannot be developed without addressing the brain's energy needs. Based on this knowledge, and to initiate thinking on potential BG therapies, a first attempt is made at hypotheses for potential control of the in vivo brain demand as well as the available in vivo BG. The aim is to adversely affect primary as well as metastatic tumours without damaging brain and innocent bystander cells.     

Acute pyogenic iliopsoas abscess in Taiwan: clinical features, diagnosis, treatments and outcome

OBJECTIVES: To study the variations of aetiology in the patients with acute pyogenic iliopsoas abscess and identify the appropriate diagnostic modalities as well as therapeutic alternatives (e.g. extraperitoneal or retrofascial percutaneous catheter drainage, PCD) other than surgery. METHODS: We carried out a retrospective review and analysis of 25 patients with acute pyogenic iliopsoas abscess in our institution from August 1988 to July 1998. Blood and urine cultures, imaging studies of the plain films of the abdomen (KUB), ultrasonography (echo) and computed tomography (CT scan) were performed in all patients. The therapeutic regimens included antibiotics only, PCD or aspiration, and surgery. RESULTS: The male to female ratio was 7: 18. The mean age was 64 years old. Diabetes mellitus (64%) was the dominant predisposing or associated factor. The most common aetiological source was urinary tract infection (52%) with enteric micro-organisms (Escherichia coli: 44% and Klebsiella spp.: 24%). Nineteen patients (76%) had pain in the abdomen, flank or back. Six cases (24%) were classified as 'primary' abscess, and only two patients survived. Nine cases were treated with antibiotics alone, only four responded and the others expired. Of the 15 cases receiving PCD or aspiration, five cases received subsequent surgical drainage or nephrectomy and survived. Another one case of Clostridia gas gangrene received emergency fasciotomy and expired. The total mortality was extremely high (11/25, 44%). CONCLUSIONS: We concluded that: (i) the aetiology of iliopsoas abscess may vary with the country of origin, with a preponderance of urinary tract infection in our Taiwanese series; (ii) a high index of suspicion is mandatory to enable early diagnosis of acute pyogenic iliopsoas abscess, particularly for older diabetic patients with fever, pain in the abdomen or flank, limp or flexion of the ipsilateral hip; (iii) CT scan can confirm the diagnosis and define the extent of the abscess; (iv) effective management should include appropriate antibiotic therapy and drainage of the abscess; (v) image-guided PCD should be tried first because of its low morbidity. However, should it fail, subsequent surgical drainage should be performed.     

Recurrent emphysematous pyelonephritis

Emphysematous pyelonephritis (EPN) is an uncommon but necrotizing renal infection due to gas-forming coliform bacteria that usually occurs in patients with diabetes mellitus and/or obstructive uropathy. Bilateral EPN is rarely seen and recurrent infection in different kidneys has never been reported in the literature. Here we present a female diabetic patient who experienced two episodes of EPN in different kidneys within 2.5 years, resulting in death eventually. We discuss the pathogenesis, incompatibility between clinical features and radiological findings of EPN, and the principle of management for this life-threatening infection.