Psoralen Isolated from the Roots of Dorstenia psilurus Welw. Modulate Th1/Th2 Cytokines and Inflammatory Enzymes in LPS-Stimulated RAW 264.7 Macrophages.

Dorstenia psilurus is a widely used plant spice in traditional African medicine to treat pain-related conditions. However, the anti-inflammatory mechanisms underlying this activity and the main active ingredients of D. psilurus have not yet been fully characterized. This study aimed to isolate and identify the main active anti-inflammatory constituents of the D. psilurus extract and to investigate the underlying anti-inflammatory mechanisms in murine macrophages. Chromatographic techniques and spectroscopic data were used for compound isolation and structure elucidation. The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and 15-lipoxygenase activity, respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit, and Th1/Th2 cytokine measurement was performed using a flow cytometer. The results indicated that the extract and fractions of D. psilurus inhibit NO production and proliferation of RAW 264.7 macrophage cells. Bioguided fractionation led to the identification of psoralen, a furocoumarin, as the main bioactive anti-inflammatory compound. Psoralen inhibited NO production and 15-lipoxygenase activity and reduced pro-inflammatory Th1 cytokines (IFN-γ, TNF-α, and IL-2) while increasing the secretion of anti-inflammatory cytokines (IL-4, IL-6, and IL-10) in activated RAW 264.7 macrophage cells. The encouraging results obtained in this study suggest that psoralen-based multiple modulation strategies could be a useful approach to address the treatment of inflammatory diseases.

Disease-specific quality of life in patients with diabetic neuropathy.

OBJECTIVES: To compare health-related quality of life (HRQoL) among patients with diabetes mellitus (DM) and diabetic neuropathy (DN) (D+N) with patients with DM without DN (D-DN) and healthy participants. To evaluate factors associated with poor HRQoL in patients with DN. METHODS: This study included 306 participants residing in Bisha, Saudi Arabia. Patients with DM were screened for DN using the Michigan Neuropathy Screening Instrument. Neuropathy severity, disability and HRQoL were determined using the Neuropathy Severity Scale (NSS), the Neuropathy Disability Score (NDS), and the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) tool, respectively. Nerve conduction studies (NCSs) were also performed. RESULTS: The D+DN group had poorer overall and domain HRQoL scores compared to the D-DN group (p<0.001). There was a strong correlation between overall HRQoL score and both NDS and NSS scores in the D+DN group (ρ= -0.71 and p<0.0001; ρ= -0.81 and p<0.0001, respectively). There was also a significant difference in all mean HRQoL domain scores between D+DN participants with normal and abnormal NCS. Physical inactivity (p=0.043), duration of DM (p<0.0001), abnormal NCS, NSS (p<0.0001), and NDS (p<0.0001) predicted HRQoL in the D+DN group. CONCLUSION: D+DN participants had a worse HRQoL compared with D-DN and healthy counterparts. NDS, NNS, physical inactivity, abnormal NCS, and duration of DM independently predicted poor HRQoL in D+DN participants.

Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male.

Light chain deposition disease (LCDD) is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 µmol/L which came down to 194 µmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

Peculiarities of tuberculosis in kidney transplant recipients.

Renal transplant is becoming increasingly available in developing countries. Significant advances have been made globally since the first successful kidney transplant in 1954, with the advent of newer, more effective and more selective immunosuppressants. As a result, allograft and patient survival has increased, leaving infection and malignancy as major challenges. The incidence rate of tuberculsis in renal transplant recipients is directly proportional to the prevalence in the general population with the developing countries having the highest rates. The objective of this paper is to review the existing literature on post renal transplant tuberculosis with a view to highlighting its peculiarities compared to tuberculosis in the general population. Several databases (Medline, EMBASE, Cochrane data base, Google Scholar and AJOL) were searched for articles using the key words Tuberculosis (MESH), Renal (OR Kidney), AND transplant. Hand search was also made of reference list of retrieved articles. Full text of relevant original articles were retrieved and appraised. Several studies have demonstrated increased risk of tuberculosis in renal transplant recipients, especially in developing countries. Tuberculosis in renal transplant recipients has peculiarities such as difficulty in diagnosing latent TB, atypical presentations, increased risk of dissemination, increased mortality and interactions of anti-Tb drugs with transplant medications. Clinicians managing renal transplant recipients especially in developing countries should have a high index of suspicion for TB and be aware of its peculiarities in this patient population.

Commercial kidney transplantation: trends, outcomes and challenges-a single-centre experience.

BACKGROUND/OBJECTIVE: Many experts believe that commercial organ transplants continue unabated despite international efforts to curb them. The aim was to determine the trends, outcomes and challenges of commercial living unrelated renal transplants (LURT) as seen in our institution. MATERIALS AND METHODS: A retrospective study of LURT patients on follow-up at our institution. The list of all LURT patients was obtained from our renal registry. Inclusion criteria for the study were 1) Presentation to our hospital within the first month post transplant; 2) Completion of one-year follow-up OR patient or allograft losses prior to completing one-year follow-up. SPSS 17.0 was used for data analysis. RESULTS: Forty-five patients satisfied the entry criteria; 33 males and 12 females with age range 13-68 years, and mean ± SD of 40 + 15 years. The majority (28) of the transplants were carried out in Pakistan, the remaining in Egypt, Philippines, and China. There has been a steady decline in the number of new patients with commercial transplants over a four-year period. Complications encountered included infections in 19 (42.2%) patients, biopsy-proven acute rejections in nine patients (20%), surgical complications in 10 patients (22.2%), post-transplant diabetes in seven (15.6%), delayed graft function in one (2.2%), and chronic allograft nephropathy in one (2.2%) patient. Patient survival at one year was 97.8% and allograft survival was 88.9%. CONCLUSIONS: Commercial kidney transplant is on the decline as seen in our center, likely as a result of international efforts to curb it, as well as due to a parallel increase in renal transplants in the country. One-year patient and allograft survivals are good but there is a relatively high rate of infections.

Concurrent Kaposi's sarcoma, tuberculosis, and allograft dysfunction in a renal transplant patient.

The major long-term complications of renal transplantation (RT) include cardio-vascular disease, opportunistic infections, malignancies, and chronic allograft nephropathy. Long-term complications are generally considered as those occurring more than 1 year post trans-plantation; however, some of the complications can occur earlier. We present a 58-year-old man who presented with multiple complications of RT concurrently and relatively early post trans-plantation including Kaposi's sarcoma, tuberculosis and allograft dysfunction.

Amyloidosis and vascular thrombosis.

Amyloidosis is a rare systemic disorder of protein metabolism with progressive extra-cellular deposition of insoluble fibrillary protein, disorganization of tissue architecture, and subsequent organ dysfunction. Primary amyloidosis is the most common form of this disorder, however, it can develop secondary to plasma cell dyscrasias such as multiple myeloma (MM); 10-15% of MM patients may develop amyloidosis of vital organs. Amyloidosis is usually associated with bleeding, but less commonly with thrombosis. We present a 52-year-old Saudi female with amyloidosis secondary to multiple myeloma. She presented with both venous and extensive arterial thrombosis. Although relatively rare, plasma cell dyscrasias such as amyloidosis and multiple myeloma could present with thrombotic rather than hemorrhagic complications.

AIDS mortality in a tertiary health institution: A four-year review.

Africa contains 70% of adults and 80% of children living with AIDS in the world and has buried 75% of the 21.8 million worldwide who have died of AIDS since the epidemic began. Nigeria, the most populous country in Africa, has 5.8% of her adult population having HIV infection at the end of 2003. We reviewed the causes of death among AIDS patients in Aminu Kano Teaching Hospital Kano, Nigeria over four years. Four-hundred-fifty-five (9.9%) of the 4,574 adult medical admissions were due to HIV/AIDS-related diagnosis. HIV/AIDS admissions increased progressively from 45 cases in 2001 to 174 in 2004. HIV/AIDS caused 176 deaths over the period giving an HIV-related mortality of 38.7%. This also showed a gradual increase from 24 deaths in 2001 to 61 deaths in 2004. The most common causes of death were tuberculosis (33.4%), septicemia (23.8%), advanced HIV disease (9.1%), meningitis (7.4%), other pulmonary infections (5.1%) and Kaposi's sarcoma (4.5%). The present dismal situation of patients living with HIV/AIDS calls for enhanced strategies to decrease the mortality trend observed. With the introduction of affordable highly active antiretroviral therapy (HAART) in several centers in Nigeria, it is hoped that infected patients can be made to live longer.