Current Topics in Medicine and Medical Research Vol. 1

A novel prophylactic regimen is demanded for preventing bladder cancer recurrence, because of the high side-effect tolls of conventional adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy, in addition to its only moderate efficacy. In vitro and animal studies have demonstrated the anti-cancer properties of a medicinal mushroom called Ganoderma lucidum (GL). In this study, a pre-malignant human uroepithelial cell (HUC-PC) and malignant mouse bladder (MB49) cell models were utilized to compare the effectiveness between ethanol extract of GL (GLe) and BCG on interleukin-6 (IL-6) secretion and lactate dehydrogenase (LDH) cytotoxicity. Additionally, parameters relevant to the BCG efficacy and safety, including free soluble fibronectin (FN) and cell-surface glycosaminoglycans (GAGs) levels were tested, following the exposure of GLe to the cells. GLe at 100 μg/ml and BCG at 4.8 × 10⁷ CFU were shown to induce equivalent levels of IL-6 in HUC-PC cells, suggesting the potential synergism. GLe have also exhibited cytotoxic effects in both cell lines. During the initial four hours of GLe exposure, the free FN concentrations in harvested media were significantly reduced that might facilitate the binding of BCG for uroepithelial internalization to enhance BCG efficacy. Furthermore, the cell membrane-bound GAGs levels of HUC-PC cells were increased in response to GLe to suggest cellular protection from BCG infection. In summary, current findings suggest the potential additive synergism of GLe with the BCG efficacy, as well as its protective effects, and thus reducing the BCG toxicity. These support the recently reported in vivo tumor inhibitory effects of GLe exhibited in the MB49/C57 bladder cancer mice model.

Purpose: The aim of our study was to assess the clinical effectiveness of topical adipose derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by comparing epithelial repair, inflammation and histological analysis between treatment arms.

Methods: Corneal lesions were performed on both eyes of 40 mice by laser induced photorefractive keratectomy. All eyes were treated with topical azythromycin bid for 3 days. Mice were divided in three treatment groups (n = 20), which included: Control, stem cells and basic serum; which received topical treatment 3 times daily for 5 consecutive days. Biomicroscope assessments and digital imaging were performed by two masked graders at 30, 54, 78, 100 and 172 h to analyze extent of fluorescein positive epithelial defect, corneal inflammation, etc. Immunohistochemical techniques were used in fixed eyes to assess corneal repair markers Ki67, α Smooth Muscle Actin (α-SMA) and E-Cadherin.

Results: The fluorescein positive corneal lesion areas were significantly smaller in the stem cells group on days 1 (p < 0.05), 2 (p < 0.02) and 3. The stem cell treated group had slightly better and faster re-epithelization than the serum treated group in the initial phases. Comparative histological data showed signs of earlier and better corneal repair in epithelium and stromal layers in stem cell treated eyes, which showed more epithelial layers and enhanced wound healing performance of Ki67, E-Cadherin and α-SMA.

Conclusions: Our study shows the potential clinical and histological advantages in the topical ADSC treatment for corneal lesions in mice.

Mortality in chronic kidney disease remains high, particularly among the elderly, who represent the most rapidly growing segment of the end-stage renal disease population in wealthier countries. The management of older adults with chronic kidney disease has become a clinical challenge and care for those patients expected to progress to end-stage renal disease should focus on evaluating the overall benefit of offering renal replacement therapy to them. Predictive mortality models may help to inform shared decision-making in the trajectory of the elderly with chronic kidney disease. This review discusses current literature on the available predictive models for predicting survival in elderly chronic kidney disease patients and reflects the author’s own interpretation and experience.

Epilepsy is a chronic disease occurring in approximately 1.0% of the world’s population. About 30% of the epileptic patients treated with available antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, it has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and Therapeutic Drug Monitoring (TDM) in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.

The pharmacokinetic (PK) and bioequivalence (BE) studies of two formulations of azelastine (AZ) was carried out in 18 healthy male Korean volunteers according to a randomized crossover-design and were performed by a new validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for quantitative analysis of plasma AZ. Subjects were given single dose of 2 tablets of 1 mg AZ of each formulation with 240 ml of water to subjects on 2 treatment days separated by one week washout period. After dosing, serial blood samples were collected for a period of 96 hours. AZ and the clomipramine (IS) were separated using a mobile phase of acetonitrile-5 mM NH₄AC (8：2, v/v, pH=6.4) with flow rate of 0.25 ml/min over Luna C18 column. Analysis required 0.2 ml of plasma and involved a solid extraction with an Oasis HLB cartridge by on-line clean-up extraction automation system and then directly injected into HPLC with an API 3000 MS system by multiple reactions monitoring (MRM) mode. Several PK parameters (including AUC_0-t, AUC_0-infinity, C_max, T_max, T_1/2 and Ke) were determined from the plasma concentration of AZ of both formulations. The AUC and C_max was tested for BE after log-transformation of the data. The ionization was optimized using ESI (+) and selectivity was achieved by MS-MS analysis, m/z 112.0 and m/z 86.1 for AZ and IS, respectively. The calibration curves with r²＞0.999 were linear over a working range of 20∼2000 pg/ml. No endogenous compounds were found to interfere with the analysis. The inter- and intra-day accuracy was in the ranges of 89.9∼109.3% and precision of inter- and intra-day expressed as relative standard deviation were 2.73∼8.79 %. No significant difference was found based on ANOVA; 90% confidance intervals (91.77∼101.94% for AUC_0-t; 90.44∼ 106.27% for AUC_0-infinity; 92.22∼108.57% for C_max) for the test and reference drugs were found within FDA guideline of 80∼125%. Based on these statistical considerations, it was concluded that test drug was bioequivalent to the reference drug and therefore, may be interchangeably in the management of allergic or bronchial asthma and prophylaxis of mucositis due to cancer chemoradiotherapy. This validated method was found to be good performance on PK and BE studies for AZ. (Cancer Prev Res 12, 84-91, 2007).

Nuclear spin possessing isotopes (²⁵Mg, ⁴³Ca, ⁶⁷Zn) promote the marked magnetic isotope effects (MIE) on DNA Polymerase Beta (DNApolB) in ex vivo survived human retinoblastoma (RB) cells. In Aphidicolin chase experiment, the RB in situ catalytic activity of DNApolB has been selectively estimated as a function of MIE. A resulted enzyme function breakdown leads to a sharp decrease of cancer cell viability. This study a paramagnetic chemotherapy path is all about.

Case Report: A previously healthy 4.5-year-old boy was admitted to our department with a 6-week history admitted to our department with a 6-week history of intermittent abdominal pain, poor appetite, sporadic nonbilious vomiting, and occasional constipation. A weight loss of five kilograms since the onset of symptoms was reported. On admission, the weight of the patient was 15 kg, as opposed to 20 kg six weeks earlier. Physical examination revealed a soft and mildly distended abdomen. A palpable, tender, round mobile mass was detected at the epigastrium. The white blood cell count was 11.000/μL (normal range, 4.500–9.900/μL), hemoglobin was 12.1 g/dL, and platelets were 420.000/μL. The serum chemistry profile was within normal limits, apart from C-reactive protein of 0.8 mg/mL (normal range, 0– 0.5 mg/mL). Abdominal ultrasonography in transverse view revealed alternating hypoechoic and hyperechoic bowel walls suggesting the target sign (Fig. 1). Hydrostatic reduction was attempted, without success (Fig. 2). Exploratory laparotomy through a right upper quadrant transverse incision revealed an ileocolic intussusception extending up to the transverse colon (Fig. 3(a)). The duodeno-jejunal junction was found to be on the right of the superior mesenteric vessels; the ileocecal junction was freely mobile and the colon was suspended by primitive mesenteric folds. Furthermore, well-defined Ladd’s bands were seen to extend from the ascending colon to the posterior abdominal wall across the duodenum (Fig. 3(b)). The intussusception was manually reduced, and no leading point was found. Ladd’s procedure was also performed including appendicectomy. The child had an uneventful recovery. Six months after the operation he was well without any further abdominal symptoms and had gained weight.

A 4.5 –year-old boy with clinical presentation and intraoperative findings described above has a chronic intussusception with intestinal malrotation that could possibly represent a variation of Waugh’s syndrome (WS). WS is usually the association of acute intussusception with intestinal malrotation. This chapter will review the history, epidemiology, pathogenesis, terminology, diagnostic evaluation and management options of acute intussusception, intestinal malrotation, chronic intussusception and WS.

The aim of this study was to investigate the effect of curcumin, indomethacin, curcumin and naproxen combination synergistically on the growth of HT-29 cells. The growth of HT-29 cells was examined by MTS cell viability assay by one to four days’ treatment with curcumin (10∼50 μM), indomethacin (250∼1,000 μM), curcumin (10∼50 μM) and naproxen (250∼1,000 μM) to 2×10⁴ HT-29 cells/mL. The results suggested that curcumin inhibited the growth of HT-29 cells in a dose-dependent fashion. In concentration range from 500 to 1,000 μM, indomethacin inhibitied the growth of HT-29 cells in a dose-dependent fashion. To examine inhibitory administered or give of curcumin and indomethacin, curcumin and naproxen combinination on the HT-29 cell lines, we treatment with 20 μM curcumin and indomethacin (500 μM, 750 μM) combinination curcumin and naproxen (750 μM, 1,000 μM) combinination to 2×10⁴ HT-29 cells/well. The results suggested that curcumin potentiates the inhibitory effect of indomethacin on the growth of HT-29 cell lines by shifting the dose-dependent manner.

MicroRNAs (miRNAs), a large family of short noncoding RNA sequences, modulate gene expression and regulate a wide range of biological processes as cell differentiation, proliferation and development, cell-to-cell communication, cell metabolism and apoptosis. There is evidence that miRNAs may have a role in molecular mechanisms linked to cellular pathways of certain diseases, as viral infections, cancer, diabetes and cardiovascular disease. miRNAs are contained in tissue cells but they are also detectable in extracellular sites, as plasma and other body fluids so they may be identified and quantified in the circulating blood by several techniques. The potential of circulating miRNAs as stable blood-based biomarkers for some diseases is described in this updated review. There are currently no circulating miRNAs that are validated as biomarkers for routinary use in daily clinical practice; lack of significant comparative studies between miRNAs and disease common biomarkers and high detection costs are the main limitations to use these nucleotides in daily clinical practice. In the near future, larger, comparative, long-term and randomized controlled trials must be undertaken to validate these disease biomarkers. 

In medicine, the search for the cause of a disease has been critical to understanding the nature of the disorder and an important step towards the discovery of effective therapies and prevention. The search for a cause is more difficult than it may seem at first. For example, even if we find the mechanism by which the disease progresses, the questions would be: What started the process; then, if we have found the factors that initiated the process that will lead to questions as to what happened to this person, and at this very moment. The answer to research questions often raises more questions and that is how research progresses.

Communication between the immune system and the Central nervous system (CNS), essential for maintaining homeostasis, is exemplified by cross-talk between glia and neurons. While actively microglia cells are modulated by neurons in the healthy brain, little is known about the cross-talk between oligodendrocytes and neurons. Oligodendrocytes, the myelin-forming cells in the CNS, are essential for the propagation of potentials action along axons, and additionally they serve to support neurons by neurotropic factors. In demyelinating diseases, such as multiple sclerosis, oligodendrocytes are thought to be the victims. Also they have strong immune functions, express a wide variety of innate immune receptors, produce and respond to the chemokines and cytokines and modulate immune responses. In Addition, they elicit responses that cause progressive neurodegeneration. Under certain circumstances cells cross the blood brain barrier and reach the parenchyma, activating a cascade of events culminating in an inflammatory lesion and demyelization. The main participants of these attacks are the CD4+T cells, antigen presenting glia (microglia and astrocytes), macrophages and B cells. On the other hand further evidence support that the beginning of autoimmune response is initiated within the CNS; we should consider other theories to explain not only multiple sclerosis as an autoimmune disease, and that starts outside the central nervous system. There is an intimate relationship that we must pay more attention in our research: The dialogue neuron-glia; the cross-talk between oligodendroglia, microglia and neuron help us to uncover novel pathways in the brain.

Background: Fat embolism syndrome (FES) is a multi-organ dysfunction caused by the fat emboli. The diagnostic of FES remains a challenge for clinicians. The clinical criteria although universally used for diagnosis of FES are not specific. Imaging studies are increasingly used in the patients with presumed FES. The aim of this chapter is to determine whether there is a correlation between the clinical parameters and the imaging findings in confirming the FES diagnosis.

Methods: All patients admitted with FES to the surgical intensive unit were enrolled in this study. Patient's demographic data, admission diagnosis, associated injuries, comorbid conditions, time to deteriorate, surgical duration, clinical manifestations, imaging findings and outcome were recorded. Data was entered into the SPSS program and required tests were applied for comparisons and p value <0.05 considered as significant.

Results: A total of 81 patients were enrolled in this study. Majority of patients (51/63%) were young male and without comorbidity (58/71.6%). About a half of the patients (49.4%) underwent intramedullary nailing for long bone fracture. Respiratory insufficiencies occurred in 98% patients and of them 11.1% had diffuse alveolar hemorrhage. Neurological deterioration was seen in 70% of the patients while the petechial skin rash was rare (2.5%). All patients had an abnormal chest x-ray but chest computerized tomography scan (CT) showed patchy alveolar opacities in 49 (60.5%) of them. Cerebral edema was a common finding in the CT brain while the brain magnetic resonance imaging (MRI) revealed a typical star field appearance in 28.4% of the patients. There was a significant correlation (P < 0.05) between the major and minor clinical criteria components and abnormal imaging findings.

Conclusions: The FES is common in young males with long bone fractures. Respiratory distress and neurological deterioration were common presentations. We suggest that the patients with suspected FES by clinical criteria, should have imaging studies to confirm the diagnosis.

The Orf disease, also known as contagious ecthyma, is a zoonotic infection caused by a dermatotropic parapoxvirus that commonly infects small ruminants such as sheep and goats. It is transmitted to humans through contact with an infected animal or fomites. Human infection typically is associated with occupational animal contact. We resently treated a healthy 41-year-old woman who presented a hangnail lesion on the middle finger of her right hand. The lesion was hard cauliflower-like mass, granulomatous and painful. Surgical debridement and biopsy were performed for further investigation. The Orf disease is usually self-limiting and resolves in 6 – 10 weeks, but complications may occur. The diagnosis may be confirmed by electron microscopy, conventional histopathology or by isolation of the virus by PCR. Early clinical recognition and knowledge of this benign viral condition are vital to avoid unnecessary surgical intervention.

Approximately 5 to 10 percent of all skin cancers occur in the periocular region. Basal cell carcinoma is the most frequent malignant periocular tumor, followed by squamous cell carcinoma, sebaceous gland carcinoma, and malignant melanoma. Nonmelanoma skin tumors at the periocular area often cause disfigurement with destruction of soft conjunctival tissue. Many therapeutic methods have been recommended to combat the morbidity and mortality associated with these lesions. Excisions with frozen-section control or Mohs micrographic surgery are regarded as the gold-standard treatments for periocular basal cell and squamous cell carcinomas. However, these treatment modalities have various limitations and reconstruction surgery is often associated with these treatment options. The chemotherapeutic agents solasodine rhamnosides in a cream formulation Curaderm^BEC5 are specific, effective and safe treatments for nonmelanoma skin cancers with excellent cosmesis. The antineoplastic mode of action is by apoptosis. In this review it is shown that Curaderm^BEC5 also treats periocular basal cell carcinoma and squamous cell carcinoma with impressive cosmetic outcomes and no reconstructive surgery is required.