Selective cytotoxicity of pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds.

BACKGROUND: Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substituted crinane skeleton. RESULTS: Our results indicate that AMD5 has efficacy and selectivity similar to PST, albeit at a 10-fold increased concentration. Interestingly AMD4 lacks apoptotic activity. CONCLUSION: Our results indicate that the phenanthridone skeleton in natural Amaryllidaceae alkaloids may be a significant common element for selectivity against cancer cells; furthermore, the configuration of the methoxy-side groups is responsible for higher binding affinity to the target protein/s thus making for a more efficient anti-cancer agent.

Summer syncope syndrome redux.

BACKGROUND: While antihypertensive therapy is known to reduce the risk for heart failure, myocardial infarction, and stroke, it can often cause orthostatic hypotension and syncope, especially in the setting of polypharmacy and possibly, a hot and dry climate. The objective of the present study was to investigate whether the results of our prior study involving continued use of antihypertensive drugs at the same dosage in the summer as in the winter months for patients living in the Sonoran desert resulted in an increase in syncopal episodes during the hot summer months. METHODS: All hypertensive patients who were treated with medications and admitted with International Classification of Diseases, 9th Revision code diagnosis of syncope were included. This is a 3-year retrospective chart review study. They were defined as "cases" if they presented during the summer months (May to September) and "controls" if they presented during the winter months (November to March). The primary outcome measure was the presence of clinical dehydration. The statistical significance was determined using the 2-sided Fisher's exact test. RESULTS: A total of 834 patients with an International Classification of Diseases, 9th Revision code diagnosis of syncope were screened: 477 in the summer months and 357 in the winter months. In patients taking antihypertensive medications, there was a significantly higher number of cases of syncope secondary to dehydration during the summer months (40.5%) compared with the winter months (29%) (P = .04). No difference was observed in the type of antihypertensive medication used and syncope rate. The number of antihypertensives used did not increase the cases of syncope in either summer or winter. CONCLUSIONS: An increased number of syncope events was observed in the summer months among people who reside in a dry desert climate and who are taking antihypertensive medications. The data confirm our earlier observations that demonstrated a greater number of cases of syncope among people who reside in a dry desert climate who were taking antihypertensive medications during summer months. We recommend judicious reduction of antihypertensive therapy in patients residing in a hot and dry climate, particularly during the summer months.

Manual urine microscopy versus automated urine analyzer microscopy in patients with acute kidney injury.

OBJECTIVE: To examine whether a significant difference exists between the reported ranges of granular and muddy brown casts in urine specimens using manual microscopy compared with an automated urine analyzer in a cohort of patients with acute kidney injury (AKI). METHODS: Freshly voided urine specimens from 25 consecutive patients who were under evaluation by the Department of Nephrology for AKI were simultaneously examined using the iQ200 automated microscopy system and manual microscopy performed by a trained observer. We coded the results according to the number of pathological casts identified and performed a 3 × 2 Freeman-Halton extension of the Fisher exact probability test. RESULTS: Overall, the number of casts identified via manual microscopy differed significantly (P <.001) from the number identified via the automated microscopy system. CONCLUSIONS: This study provides evidence of the importance of performing a manual microscopic examination of urine sediment in patients with AKI. Further studies are needed to assess whether manual microscopy provides prognostic implications regarding renal recovery, hemodialysis dependency, and mortality.

Summer syncope syndrome.

BACKGROUND: Antihypertensive therapy is associated with significant relative risk reductions in the incidence of heart failure, myocardial infarction, and stroke. However, a common adverse reaction to antihypertensive therapy is orthostatic hypotension, dehydration, and syncope. We propose that continued use of antihypertensive medications at the same dosage during the dry summer months in patients living in the Sonoran desert leads to an increase in syncopal episodes. METHODS: All hypertensive patients who were treated with medications and admitted with International Classification of Diseases, 9th Revision code diagnosis of syncope were included. They were defined as "cases" if they presented during the summer months (May to September 2012) and "controls" if they presented during the winter months (November 2012 to March 2013). The primary outcome measure was the presence of clinical dehydration. The statistical significance was determined using the 2-sided Fisher exact test. RESULTS: A total of 496 patients with an International Classification of Diseases, 9th Revision code diagnosis of syncope were screened, and 179 patients were included in the final analysis. In patients taking antihypertensive medications, there were a significantly higher number of cases of syncope secondary to dehydration or orthostatic hypotension during the summer months (45%) compared with the winter months (26%) (P = .01). The incidence of syncope was significantly higher in older patients (63%) compared with younger individuals (37%) during the summer months. CONCLUSIONS: The incidence of syncope increases during the summer months among people who reside in a dry desert climate and who are taking antihypertensive medications. On the basis of our findings, we describe an easily preventable condition that we define as the "Summer Syncope Syndrome." We recommend judicious reduction of antihypertensive therapy in patients residing in a hot and dry climate, particularly during the summer months.