Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time type-DED is common, and stabilization of the tear film is the first goal of treatment. Treatment of DED begins with eye drops. Until now, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side effects (cataracts, increased intraocular pressure). This review evaluates the new generation of DED therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on these considerations, it is proposed that the optimal treatment for DED in Asia is the initial application of mucin secretion enhancing eye drops (long-acting diquafosol) and oral supplements, and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood-brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS=5.75 ± 0.932 L·Kg-1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially under influence of oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted previously introduced clinical model of host-virus interaction (i.e. infectious process in immunodeficiency) for analysis of B cells and specific IgG role (observational study of a CVID patient who received intravenous immunoglobulin (IVIG)) Suddenly, the patient deteriorated with positive result of HBs, HBV-DNA (369x106copies). In spite of lamivudine therapy and IVIG escalation (from 0.3 to 0.4g/kg), CT showed 11cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs had been positive in time-lapse analysis (range 111-220 IU/ml). Replacement therapy intensification was complicated by immune complex disease with renal failure. The fulminant HCC in CVID and the development of the tumor as the first sign is interesting. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HBs substitution has not been proven to be effective, oncoprotective nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, patient selection more precise with the exclusion of HBV-positive donors. Our clinical model show HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g. chronic hepatitis). Lack of cell cooperation, B cell deficiency observed in CVID plays a crucial role in high HBV replication, especially in carcinogenesis.

Microsamples (collections usually less than 50 µL) have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venipuncture. However, venipuncture remains the sampling gold standard for metabolic phenotyping of blood. This pre-sents several challenges in metabolic phenotyping workflows: accessibility for individuals in ru-ral and remote underserved areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample col-lection difficulty in the young and elderly. Furthermore, venous sample stability may be compro-mised when temperate conditions necessary for cold-chain transport are beyond control. Alter-natively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for mi-crosampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for employment of microsamples in metabolic phenotyping research. Supporting the translation of research from the ‘bench to the community’.