Vision in the common bed bug Cimex lectularius L. (Hemiptera: Cimicidae): eye morphology and spectral sensitivity.

Bed bugs as pests of public health importance recently experienced a resurgence in populations throughout the U.S. and other countries. Consequently, recent research efforts have focused on improving understanding of bed bug physiology and behaviour to improve management. While few studies have investigated the visual capabilities of bed bugs, the present study focused specifically on eye morphology and spectral sensitivity. A 3-D imaging technique was used to document bed bug eye morphology from the first instar through adult and revealed morphological characteristics that differentiate the common bed bug from the tropical bed bug as well as sex-specific differences. Electrophysiological measurements were used to evaluate the spectral sensitivity of adult bed bugs. Male bed bugs were more responsive than females at some wavelengths. Electrophysiological studies provided evidence for at least one photoreceptor with a spectral sensitivity curve peak in the green (λmax 520 nm) region of the spectrum. The broadened long wavelength portion of the spectral sensitivity curve may potentially indicate another photoreceptor in the yellow-green (λmax 550 nm) portion of the spectrum or screening pigments. Understanding more about bed bug visual biology is vital for designing traps, which are an important component of integrated bed bug management.

Pharmacokinetics of perindopril: therapeutic consequences.

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half life of over 30 hours associated with sustained inhibition of ACE. During repeated dosing there is little accumulation of drug, and no evidence of increased haemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: binding of perindoprilat to ACE prolongs the haemodynamic effect, giving the option of once daily administration; despite the long terminal elimination half life of the drug, significant accumulation is not a problem during chronic treatment; increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used; further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.

Pharmacokinetics of perindopril: therapeutic consequences.

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half-life of over 30 hours, associated with sustained inhibition of ACE. During repeated dosing, there is little accumulation of the drug and no evidence of increased hemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: (1) Binding of perindoprilat to ACE prolongs the hemodynamic effect, giving the option of once daily administration. (2) Despite the long terminal elimination half-life of the drug, significant accumulation is not a problem during chronic treatment. (3) Increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used. (4) Further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.

The in vivo distribution of methotrexate between plasma and erythrocytes.

1. The concentration of methotrexate in whole blood, plasma and erythrocytes was measured in three patients receiving 250 mg methotrexate by continuous intravenous infusion over 12 h for different malignant diseases. 2. Methotrexate was measured using a double-antibody radioimmunoassay which facilitated drug monitoring for 1--2 weeks. 3. The concentration of methotrexate in plasma was much higher than that in whole blood and erythrocytes during the period of infusion, but this profile was reversed during the elimination phase. 4. The concentration in erythrocytes fell rapidly immediately after the infusion ended, but thereafter, in contrast to plasma levels, methotrexate concentrations in erythrocytes did not appear to decay during the elimination phase. In one patient the concentration/time profiles differed between treatment days. On the first occasion, at the initiation of chemotherapy, erythrocytes progressively accumulated methotrexate in the elimination phase against an apparent concentration gradient. On the second occasion this progressive increase was not observed, but as in the other two patients, methotrexate levels in red cells remained many times higher than drug levels in plasma throughout the period of observation. 5. Folinic acid administration did not appear to influence the distribution of methotrexate between red cells and plasma. 6. It was concluded that while the distribution between plasma and erythrocytes was probably mediated by complex mechanisms, the results were consistent with the erythrocyte mass behaving as a slowly exchanging kinetic compartment. Accumulation and persistence of a drug such as methotrexate in red cells might be expected to promote resistance and perhaps influence the expression of toxicity.

The protein binding of methotrexate in the serum of patients with neoplastic disease.

1. Serum protein binding of methotrexate was studied in 14 patients with various forms of malignant disease and in eight age- and sex-matched subjects (control group) attending outpatient clinics for various clinical conditions. 2. Protein binding was determined by continuous ultrafiltration and methotrexate concentrations by double-antibody radioimmunoassay. 3. Protein binding of the drug is critically dependent on albumin concentration, as shown by results in individual subjects and a significant regression of methotrexate binding on albumin concentration. Moreover, at high methotrexate concentrations drug binding becomes non-linear, resulting in disproportional elevation of free methotrexate levels. Both these findings have important implications for the treatment of hypoalbuminaemic patients. 4. Two classes of binding sites were observed in both groups of patients, viz a high-affinity, low-capacity group and a low-affinity group with higher capacity. 5. No significant difference was found between patient and control groups either in the percent bound drug or in the binding parameters. 6. In conclusion, while there appear to be no factors specific to malignant disease which perturb methotrexate's protein binding, it may be important to determine the extent of drug binding before methotrexate can be used judiciously, particularly when total drug level is related to likely toxicity and in the design of an appropriate folinic acid rescue regimen after high-dose therapy.

Genetic manipulation by means of microcell-mediated transfer of normal human chromosomes into recipient mouse cells.

Microcell-mediated chromosome transfer is an innovative approach to the production of karyotypically simple hybrids. This method of gene transfer, employing micronuclei formed by prolonged Colcemid treatment, has been utilized for rodent systems. Expansion of this technology to include transfer of normal human genetic material has been hindered because large micronucleate populations from diploid human cells have been unobtainable. This report describes the production of micronuclei in 40-60% of normal human fibroblasts. These micronucleated cells have been enucleated by combining centrifugation and cytochalasin B treatment, and the resultant microcells have been purified and fused to recipient mouse (LMTK-) cells. Microcell hybrid clones containing a single human chromosome have been isolated from three separate fusion experiments. The time course for production of these hybrids, from fusion to karyotypic analysis, was 6 weeks. With a transfer frequency of about 2 x 10(-6), a single intact human chromosome has become a functioning element of the murine genome.

Dose dependent methotrexate elimination following bolus intravenous injection.

The pharmacokinetics of methotrexate have been assessed at two dose levels in six patients receiving the drug for treatment of malignant disease. Each patient received bolus intravenous doses of 25 mg and 100 mg given at least one week apart, the order of administration being random. Blood and urine were collected until 48 h for methotrexate analysis by radioimmunoassay and data analysed by a model-independent pharmacokinetic approach. In each patient area under the methotrexate serum concentration-time curve (o to chi) increased out of proportion to the increase in methotrexate dose. This was reflected in a mean clearance value after the 100 mg dose of 31 +/- 16 (SD ml x min(-1) compared with a mean clearance of 62 +/- 19 ml x min(-1) following injection of 25 mg methotrexate. Renal clearance of methotrexate was markedly lower following the 100 mg dose (18 +/- 6 ml x min(-1) than after 25 mg (53 +/- 19 ml x min(-1). Saturation of the proximal tubular organic acid transport system is the likely cause of methotrexate's capacity limited elimination.

The protein binding of methotrexate by the serum of normal subjects.

The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37 degrees C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16 +/- 0.05 (S D) binding sites with an intrinsic association constant of 71.15 +/- 35.98 (S D) X 10(4) M-1: Class II had 2.01 +/- 0.93 (S D) binding sites and and affinity of 0.18 +/- 0.15 X 10(4) M-1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 muMol 1-1.

Enhancement of methotrexate absorption by subdivision of dose.

A comparison was made in fasting patients between a single 100 mg oral dose of methotrexate formulated as its sodium salt in a palatable syrup and the same total quantity of drug administered in four divided doses of 25 mg taken at 2-h intervals. Allocation to the order of these treatment schedules was on a random basis. The area under the serum methotrexate concentration-time curve until 50 h was found to be considerably greater after the divided dose regimen, the mean ratio AUC 25 mg x 4/AUC 100 mg being 1.86 (+/- 0.90). There was no significant difference in peak serum methotrexate concentrations or methotrexate half-life estimates between the two regimens, however. The results of this study are consistent with saturation of an intestinal transport process when methotrexate is administered orally in a single large dose.