Kagimminols A and B, Cembrene-Type Diterpenes from an Okeania sp. Marine Cyanobacterium.

Kagimminols A (1) and B (2), new cembrene-type diterpenoids, were isolated from an Okeania sp. marine cyanobacterium. By combining DP4 analysis with an efficient NMR chemical shift calculation protocol, we clarified the relative configurations of 1 and 2 without consuming precious natural products. We determined the absolute configurations by a comparison of theoretical electronic circular dichroism (ECD) spectra with experimental spectra, and the absolute configuration of 1 was verified experimentally. Finally, we found that 1 and 2 showed selective growth-inhibitory activity against the causative agent of human African trypanosomiasis. This study exemplifies that computational chemistry is an efficient tool for clarifying the configurations of natural products possessing tautomers in equilibrium.

Isolation and Total Synthesis of Bromoiesol sulfates, Antitrypanosomal arylethers from a Salileptolyngbya sp. Marine Cyanobacterium.

Bromoiesol sulfates A (1) and B (2), new polyhalogenated aryl sulfates, were isolated from a Salileptolyngbya sp. marine cyanobacterium along with their hydrolyzed compounds, bromoiesols A (3) and B (4). To pick up the candidates of their structures, we used Small Molecule Accurate Recognition Technology (SMART), an artificial intelligence-based structure-prediction tool, and their structures were elucidated on the basis of single-crystal X-ray diffraction analysis of bromoiesols (3 and 4). In addition, to verify the structures, the total synthesis of bromoiesol A sulfate (1) and bromoiesol A (3) was achieved. The bromoiesol family, especially bromoiesols (3 and 4), selectively inhibited the growth of the bloodstream form of Trypanosoma brucei rhodesiense, the causative agent of human African sleeping sickness.

Early diagnosis of cerebral ischemia in cerebral vasospasm by oxygen-pulse near-infrared optical topography.

PURPOSE: Early diagnosis of vasospasm is a key factor in the choice of treatment after subarachnoid hemorrhage (SAH). However, a noninvasive method of diagnosing delayed ischemic neurological deficit (DIND) has not been established. We therefore propose a new method of diagnosing cerebral ischemia using near-infrared optical topography (OT) with oxygen inhalation. MATERIALS AND METHODS: We used a 44-channel OT system that covers the bilateral front otemporoparietal areas to assess 29 patients who underwent surgery within 72 h of the onset of SAH. The patients inhaled room air followed by oxygen for 2 min, and then peripheral oxygen saturation (SpO2) was continuously monitored at the index fingertip. The patients were assessed by N-isopropyl-p-[¹²³I]iodoamphetamine (IMP)-SPECT and OT on the same day. Ischemic findings were confirmed using principal component analysis with reference to the systemic SpO2value. RESULTS: Seven of 29 patients developed DIND. Evidence of ischemia was identified by OT in all seven of these patients before the onset of DIND. The OT and SPECT findings agreed in 27 (93 %) of the 29 patients. DISCUSSION AND CONCLUSIONS: Our method might detect cerebral ischemia before the onset of DIND and thus be clinically useful for assessing cerebral ischemia with vasospasm.

Analysis of muscle synergy and gait kinematics during regain of gait function through rehabilitation in a monoplegic patient.

Purpose: We conducted muscle synergy and gait analyses in a monoplegic patient whose gait function improved through training, to explore the possibility of using these parameters as indicators of training. Case presentation: A 49-year-old male had monoplegia of the right lower limb caused by infarction of the left paracentral lobule. After 2 months of training, he was able to walk and returned to work. Methods: Consecutive analyses were done after admission. Muscle synergy analysis: during walking, surface electromyograms of gluteus maximus, quadriceps femoris, adductor femoris, hamstrings, tibialis anterior, medial/lateral gastrocnemius, and soleus on both sides were recorded and processed for non-negative matrix factorization (NNMF) analysis. Gait analysis: markers were placed at foot, and walking movements were video recorded as changes in position of the markers. Results: Compared with three muscle synergies detected on the non-paretic side, two muscle synergies were extracted on the paretic side at admission, and the number increased to three and then four with progress in rehabilitation training. Changes in weighting and activity of the muscle synergies were greater on the non-paretic side than on the paretic side. With training, the knee joint flexor and the ankle dorsiflexor activities on the paretic side and the gluteus maximus activity on the non-paretic side increased during swing phase as shown by weight changes of muscle synergies, and gait analysis showed increased knee joint flexion and ankle joint dorsiflexion during swing phase in the paretic limb. On the non-paretic side, however, variability of muscle activity was observed, and three or four muscle synergies were extracted depending on the number of strides analyzed. Conclusion: The number of muscle synergies is considered to contribute to motor control. Rehabilitation training improves gait by increasing the number of muscle synergies on the paretic side and changing the weights of the muscles constituting the muscle synergies. From the changes on the non-paretic side, we propose the existence of compensatory mechanisms also on the non-paretic side. In muscle synergy analysis, in addition to the filters, the number of strides used in each analysis set has to be examined. This report highlights the issues of NNMF as analytical methods in gait training for stroke patients.

Isolation of Hennaminal and Isolation and Total Synthesis of Hennamide, Pyrrolinone Compounds from the Marine Cyanobacterium Rivularia sp.

Two new natural products were isolated from the marine cyanobacterium Rivularia sp. collected in Japan. Hennaminal possesses a very rare functional group, ß,ß-diamino unsaturated ketone, which has only been found in bohemamine-type natural products so far. Hennamide possesses a reactive N-acyl pyrrolinone moiety, which induces self-dimerization. The isolation and structure determination supported by computational chemistry and total synthesis, as well as the antitrypanosomal activities of hennaminal and hennamide are described.

Role of primary motor cortex in gait: automatic-voluntary dissociation seen in paretic leg of a patient who had a stroke.

Objective: To examine the role of primary motor cortex in gait through exploring the dissociation of impaired voluntary leg muscle contraction and preserved rhythmic activities during gait in a patient who had a stroke. Subject and methods: A 49-year-old man with an infarct in the primary motor cortex exhibited automatic-voluntary dissociation in the paretic leg. Functional studies were conducted using surface electromyography (EMG) and near-infrared spectroscopy (NIRS). Results: The patient was incapable of voluntary contraction of individual leg muscles on the paretic right side but was able to walk automatically while contracting those muscles rhythmically. Surface EMG confirmed the earlier findings objectively. The preserved automatic activities helped recovery of gait capability, but NIRS showed no functional recovery in the corresponding motor cortex during treadmill gait. We considered that the loss of voluntary leg muscle contraction and the preserved gait capacity in this patient represented a form of automatic-voluntary dissociation. Conclusions: The preserved gait capability suggests that the leg representation of the primary motor cortex may not play a major functional role in gait, but other components of the nervous system, including the spinal central pattern generator, would serve important functions to maintain gait capability.

Isolation and Total Synthesis of Beru'amide, an Antitrypanosomal Polyketide from a Marine Cyanobacterium Okeania sp.

A 68 µg amount of an acyclic polyketide, named beru'amide, was isolated from a marine cyanobacterium Okeania sp. Beru'amide contains six unique moieties in its relatively small skeleton. By applying several cutting-edge techniques, including DFT-based chemical shift calculations, we achieved the structure determination and the total synthesis of this highly functionalized scarce natural product. Furthermore, beru'amide was shown to have strong antitrypanosomal activity.

Cognitive impairment and neurovascular function in patients with severe steno-occlusive disease of a main cerebral artery.

OBJECTIVE: Patients with severe steno-occlusive disease of a main cerebral artery may demonstrate cognitive impairment without identification of causative lesions on magnetic resonance imaging. We investigated whether cognitive impairment in these patients is associated with regional cerebral blood flow (rCBF), leukoaraiosis, risk factors of atherosclerosis and cerebrovascular reserve (CVR), which shows so-called clinical neurovascular function. METHODS: In 65 patients with severe steno-occlusive disease of an internal carotid artery or a middle cerebral artery (MCA) and no cerebral infarction (CI), we examined cognitive function with COGNISTAT, grades of leukoaraiosis, and CBF and CVR as calculated by iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography and blood data. We compared such values of the left and right sided diseases. rCBF and CVR on the affected side were compared to other side. RESULTS: Logistic regression analysis revealed that CVR correlated with cognitive impairment. There was no significant difference in rCBF, CVR, or COGNISTAT score when comparing the left and right sided diseases. There were good correlations between CBF or CVR of the ipsilateral MCA area and ipsilateral and contralateral other areas. CONCLUSION: Cognitive impairment is associated with CVR in the whole brain. Nonselective widespread neurovascular mild dysfunction can be a reason for cognitive impairment in patients with severe steno-occlusive disease of a main cerebral artery and no CI.

Detection of cerebral ischemia using the power spectrum of the pulse wave measured by near-infrared spectroscopy.

The diagnosis and medical treatment of cerebral ischemia are becoming more important due to the increase in the prevalence of cerebrovascular disease. However, conventional methods of evaluating cerebral perfusion have several drawbacks: they are invasive, require physical restraint, and the equipment is not portable, which makes repeated measurements at the bedside difficult. An alternative method is developed using near-infrared spectroscopy (NIRS). NIRS signals are measured at 44 positions (22 on each side) on the fronto-temporal areas in 20 patients with cerebral ischemia. In order to extract the pulse-wave component, the raw total hemoglobin data recorded from each position are band-pass filtered (0.8 to 2.0 Hz) and subjected to a fast Fourier transform to obtain the power spectrum of the pulse wave. The ischemic region is determined by single-photon emission computed tomography. The pulse-wave power in the ischemic region is compared with that in the symmetrical region on the contralateral side. In 17 cases (85%), the pulse-wave power on the ischemic side is significantly lower than that on the contralateral side, which indicates that the transmission of the pulse wave is attenuated in the region with reduced blood flow. Pulse-wave power might be useful as a noninvasive marker of cerebral ischemia.

Evaluation of cerebral ischemia using near-infrared spectroscopy with oxygen inhalation.

Conventional methods presently used to evaluate cerebral hemodynamics are invasive, require physical restraint, and employ equipment that is not easily transportable. Therefore, it is difficult to take repeated measurements at the patient's bedside. An alternative method to evaluate cerebral hemodynamics was developed using near-infrared spectroscopy (NIRS) with oxygen inhalation. The bilateral fronto-temporal areas of 30 normal volunteers and 33 patients with cerebral ischemia were evaluated with the NIRS system. The subjects inhaled oxygen through a mask for 2 min at a flow rate of 8 L/min. Principal component analysis (PCA) was applied to the data, and a topogram was drawn using the calculated weights. NIRS findings were compared with those of single-photon-emission computed tomography (SPECT). In normal volunteers, no laterality of the PCA weights was observed in 25 of 30 cases (83%). In patients with cerebral ischemia, PCA weights in ischemic regions were lower than in normal regions. In 28 of 33 patients (85%) with cerebral ischemia, NIRS findings agreed with those of SPECT. The results suggest that transmission of the changes in systemic SpO2 were attenuated in ischemic regions. The method discussed here should be clinically useful because it can be used to measure cerebral ischemia easily, repeatedly, and noninvasively.

[Assessment of cerebral ischemia by oxygen pulse-based near-infrared optical topography].

BACKGROUND: SPECT and angiography are used to assess the cerebral blood flow dynamics; however, they have several drawbacks such as physical stress on the patients and considerable invasiveness. In order to overcome these drawbacks, we proposed and verified an alternative method of involving optical topography (OT). MATERIALS AND METHODS: We used a 48-channel OT system with the 2 faces of 3 x 5 probe-holders on the patient's head, covering the bilateral fronto-temporal areas. The study was conducted with 11 normal volunteers and 30 patients with cerebral ischemia (ICA or MCA stenosis). All measurements were performed at a constant frequency of 10 Hz. In a block fashion, the subjects inhaled room air followed by oxygen for 2 minutes and then room air again, and SpO2 were monitored at the subjects' finger tips. In some cases, IMP-SPECT was performed. RESULTS: The level of oxyhemoglobin measured by OT in the normal brain regions showed a trapezoid increase in accordance with oxygen inhalation, and similar results were obtained for SpO2. In the ischemic regions, the oxyhemoglobin increase was delayed and/or its height was lower. These observations suggest that the transmission of the systemic SpO2 wave pattern was delayed and its extent was lower in the ischemic region; this phenomenon can be utilized to detect the tissue ischemia. Principal component analysis was performed based on the SpO2 wave pattern. No lateralities were observed in 81.8% of the normal cases. However, in the ischemic cases, the weights of the principal components in the ischemic regions were reduced, and these findings agreed with the SPECT findings regarding of ischemia in 76.2% of the cases. DISCUSSIONS AND CONCLUSIONS: Our results suggested that the regional attenuation of the oxhemoglobin wave demonstrated by principal component analysis reflects the ischemic state of cerebral blood flow. This novel method uses oxyhemoglobin as an OT. It can be clinically utilized as a real-time noninvasive method for the assessment of cerebral ischemia.